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Piracetam - James South
Article - reviewing
piracetam, aniracetam, pramiracetam, and oxiracetam
by James South M.A.
Over 30 years have passed since the "Nootropic Revolution" quietly began with the development of Piracetam in the late medical efficacy with a virtual absence of toxicity and side effects; something rarely seen with more standard medical drugs.
More importantly, they offered promise not only in the realm of fighting disease, but also in the virtually unexplored realm of drugs that could not only postpone or even reverse "normal" brain aging, but could even make "normal" brains work better!
The Piracetam-nootropics have been exhaustively researched; since the first scientific studies on Piracetam in the late 1960's over 1000 scientific papers on Piracetam, Oxiracetam, Pramiracetam, and Aniracetam have been published, with about two thirds of them on Piracetam.
The action of the Piracetam-nootropics has been studied in a broad range of animals; goldfish, mice, rats, guinea pigs, rabbits, cats, dogs, marmosets, monkeys and humans.
The toxicity of Piracetam and its "cousins" is amazingly low- almost non-existent. In acute toxicity studies, intravenous doses of Piracetam given to rats (8g/ Kg bodyweight) and oral doses given to mice, rats, and dogs (10g/ Kg or more) produced no toxicity.
This would be equivalent to 560-700 grams (1.23 to 1.54 pounds) for a 154 pound human. Rats given 100-1000mg/ Kg orally for 6 months and dogs given 10,000mg/ Kg orally for one year showed no toxic effect, a teratogenic (birth defect causing) effects were found, either (Tacconi and Wurtman 1986).
The Piracetam-nootropics are among the toxicologically safest drugs ever developed.
The four main commercially available "racetam" nootropics all share a pyrrolidine nucleus, while Piracetam, Oxiracetam, and Pramiracetam, also share an acetyl group. The racetams (especially Piracetam and Oxiracetam) are closely related in structure to the amino acid Pyroglutamic Acid. Pyroglutamic Acid has been shown in some studies to have weak nootropic activity (Gouliaev and Senning 1994). Pyroglutamic Acid is naturally present in many human foods, as well as the mammalian brain.
The concept and definition of a "nootropic drug" was first proposed in 1972 by C.E. Giurgea, the principal Piracetam researcher and research coordinator for UCB, the Belgian company that launched Piracetam. "The main features... defining a nootropic drug are: (A) the enhancement, at least under some conditions, of learning acquisitions as well as the resistance of learned behaviors to agents that tend to impair them; (B) the facillitation of interhemispheric flow of information; (C) the partial enhancement of the general resistance of the brain and particularly its resistance to physical and chemical injuries; (D) the increase in the efficacy of the tonic cortico-subcortical control mechanisms; and (E) [absence of the usual negative pharmacologic effects of psychotropic drugs]." Giurgea,and Salama 1977). Giurgea derived the term "nootropic" from the i words "noos" (=mind) and "tropein" (=to turn toward).
Schaffler and Klausnitzer (1988) have given an excellent brief overview of some of the chief effects of the Piracetam-nootropics. "From animal biochemistry it is known that [Piracetam-nootropics] enhance brain metabolism by stimulation of oxidative catabolism, increcrease of ATP-turnover and cAMP levels, enhancement of phospholipid-metabolism and protein biosynthesis. [PIR-nootropics have] an impact on the hippocampal release of acetylcholine and on the dopaminergic turnover, too. Pharmacologically there exist protective effects with regard to several noxes [harmful agents] and an impact on the associative cortical sphere and on hippocampal structures, which are related with learning and memory, especially when the respective functions are impaired. The performatory enhancements are related with an increased arousability of hippocampal pyramid cells, facilitated transmission of the thalamic afferences, increased release of hippocampal acetylcholine and enhanced synaptic transmission.
The clinical biochemistry indicates enhancing functions on the utilization of oxygen and glucose under the conditions of decreased brain metabolism, as well as improvements in local perfusion. Due to this profile [Piracetam -nootropics] can be expected to be of value in the treatment of disease which are related to impairments in the above mentioned features, such as several types of senile dementia, (e.g. Primary Degenerative Dementia= Alzheimer’s type: Multi Infarct [stroke] Dementia), ischaemic [poor brain blood flow] insults, hypoxia, anoxia and toxicologically or dietary based deficiencies." (Footnotes in the original text omitted here).
From the beginning of Piracetam research, the ability of the Piracetam -nootropics to partly or completely prevent or reverse the toxic action of a broad array of chemicals and conditions has been repeatedly demonstrated. Aniracetam reverses the memory impairment in rats induced by Clonidine, Piracetam, Oxiracetam, Pramiracetam, and Aniracetam all antagonise the normally lethal neuromuscular blockade induced by Hemicholinium-3 (HC3) in mice. Piracetam, Oxiracetam, and Aniracetam have all attenuated or reversed the Scopalamine (anticholinergic agent)- induced amnesia in rats and mice under a broad range of experimental conditions.
Oxiracetam has reversed the typical "spaced out" electroencephalogram (EEG) of healthy humans given Valium, restoring a normal vigilance EEG while maintaining Valium's anti-anxiety effects. Piracetam and Aniracetam have ameliorated the amnesia produced by the protein synthesis inhibitor Cycloheximide.
Piracetam, Oxiracetam, Pramiracetam and Aniracetam all attenuate or reverse the amnesia in mice and rats induced by electroconvulsive shock treatment (ECS) in both passive and active learning conditions.
When mice were given Oxydipen+onium, a short acting curare-like agent which induces asphyxia, at a dose sufficient to kill 90-100% of the placebo treated controls, the two groups of Piracetam treated mice had a 90 and 100% survival rate.
When humans, rats, mice and rabbits have been put under diverse hypoxic experimental conditions, Piracetam, Oxiracetam, and Aniracetam have acted to attenuate or reverse the hypoxia-induced amnesia and learning difficulties. as well as to speed up recovery time from hypoxia and reduce the time needed to renormalize the EEG (Gouliaev and Senning Giurgea and Salama 1977).
A classic series of experiments on the protective power of Piracetam against barbiturate poisoning was reported by Moyersoons and Giurgea in 1974. Rabbits connected to EEG machines were given either Piracetam or saline injections before intravenous (I.V.) administration of the fast acting barbiturates-Secobarbital (SEC).
When Piracetam was given I.V. one hour before SEC, 10/10 rabbits survived versus 3/10 survivors given saline. EEG records showed only minimal abnormalities in the Piracetam rabbits, while the saline rabbits showed massive EEG silence, rapidly followed by death. When given only one-half hour before SEC, 7/11 Piracetam rabbits survived versus 3/1 1 control rabbits.
EEG records of the Piracetam rabbits showed somewhat more abnormalities than those given one hour Piracetam pre-treatment, but still far more normal appearing than the saline control rabbits' EEG's. Piracetam was also given orally one hour before SEC. 8/9 Piracetam rabbits survived while only 3/9 controls survived. The EEG records of both groups were similar to those of the rabbits given Piracetam and saline I.V. one hour before SEC.
The experiments then treated Piracetam against a more slow acting barbiturate Allobarbital (ALB), giving the Piracetam I.V. two minutes after the ALB infusion 11/13 Piracetam rabbits survived, while only 2/13 saline control rabbits survived EEG records of the Piracetam rabbits again showed electrical silences to be almost absent, and if present, to be shorter and appear later than in the control animals.
In the ALB experiment, one of the two surviving control rabbits actually presented a more normal EEG after ALB than did one of the survivors eleven Piracetam survivors..
Yet an EEG recorded the next morning (about 18 hours later) showed that the control was still asleep, and it was not aroused by a loud noise. The Piracetam rabbit, however, was well awake, behaved normally, moved around, and its EEG was normal.
Thus, whether given I.V. or orally, and before or after general lethal (to controls) barbiturate infusion, Piracetam served to protect both life and brain structure and function, as evidenced by EEG records and post recovery behavior.
The rabbit experiments just described are hardly unusual. The Piracetam -nootropics routinely show an ability to stabilise or normalise the EEG's of humans and animals under a broad range of experimental and medical conditions.
The EEG records the electro-chemical activity of large groups of cortical neurons, and thus provides a "macro" picture of brain activity. Aging, dementia, hypoxia and benzodiazepines all promote a similar shift in EEG frequency patterns.
Low frequency delta waves (0-4 cycles per second) and theta
waves (4-8 cps) are increased, while alpha waves (8-12 cps) and beta waves
(beta-1; 12-20 cps, beta 2; 20-32 cps) diminish. The average frequency of the
delta and alpha waves also drops, as compared to healthy normal subjects.
Nootropics - clinical studies
Giaguinto and colleagues (1986) gave 12 healthy humans 5mg Valium orally at 10PM the night before their experiment. The next morning they were given either I.V. Oxiracetam or saline in a double blind crossover experiment. Oxiracetam strongly decreased the excessive delta activity while simultaneously strongly increasing alpha activity, and also induced a modest increase in beta activity. Thus Oxiracetam restored the EEG to a pattern indicating increased vigilance and alertness, yet without destroying Valium's anti-anxiety effect.
Itil and co-workers (1986) treated four groups of 15 patients
suffering mild to moderate dementia with either Oxiracetam or placebo for three
months. The double
blind study used Oxiracetam in doses of 800, 1600 and 2400mg
daily. Quantitative EEG data indicated that in patients with dementia,
Oxiracetam had a mode of action similar to other vigilance enhancing compounds.
The majority of patients who had abnormal slow EEG patterns before treatment
showed a "normalization" of their brain waves- i.e. a decrease in slow
(delta and theta) and an increase in alpha waves. Saletu and colleagues ( 1985)
conducted a four week double
blind trial of Oxiracetam (2400 mg per day) or placebo in 40
patients (mean age; 80 years) suffering from the "organic brain syndrome of
late life." Their results showed a clear trend towards a decrease in delta
and theta wave activity, an increase in alpha and beta wave activity, as well as
an increase in the dominant frequency and the centroid of alpha activity after
Oxiracetam treatment.
Piracetam -nootropics have also shown the ability to improve learning and memory in healthy individuals not suffering from disease or severe age-related degeneration. In 1976 Dimond and Brouwers reported the results of some of a series of seven double blind trials, involving 16 second and third year college students "in excellent health and good physical and mental condition."
Subjects received either 4.8 grams a day Piracetam or placebo for 14 days. In three different measures of verbal learning and memory, the results showed a highly significant difference in favor of the Piracetam students over the controls, with confidence levels of P=.01, P=.02 and P=.01. The authors stated "the fact is that Piracetam improves verbal learning and in this it would appear to be a substance which is.. capable of extending the intellectual functions of man.. our subjects were not senile, suffering from generalized brain disorder, confusional states, or any other pathology of the brain... It is therefore possible to extend the power which [individuals gifted with high intelligence and good memory] possess to still higher levels despite the fact that the range of their achievement is a high."
Giurgea and Salama report the confirmation of Dimond/ Brouwer's work by Wedl and Suchenwirth in 1977. Wedl found significant improvement in mental performance in a group of 17 healthy young volunteers given 3.2 grams per day Piracetam for five days.
Mindus and colleagues (1976) reported the results of a double blind crossover trial with 18 healthy middle aged people (median age 56), with no evidence of somatic or mental disease, based on medical records and administration of several intelligence tests (group mean IQ; 120 plus or minus 11).
Most of the subjects were in intellectually demanding jobs, but had reported a slight reduction for some years in their capacity to retain or recall information.
After four weeks of 4.8 grams per day Piracetam, Piracetam subjects were switched to placebo for four weeks, while the original placebo group then received Piracetam for four weeks.
Results of a series of paper and pencil tests, as well as computerised tests to measure perceptual motor reactions, showed a clear benefit of Piracetam over placebo.
The three different paper and pencil tests showed superior effects on performance compared to placebo, with confidence levels of P<.001, P<.001 and P<.05. In four of the six computerised tests Piracetam showed a significant effect over placebo, with confidence levels of P<.05 for three and P<.029 for the fourth.
A fifth test showed a clear trend in favor of Piracetam, with P<.10. Wilsher and co-workers (1979) related their results with 4.8 grams per day Piracetam in a double blind, crossover trial to study the benefits of Piracetam for dyslexic students.
Interestingly, the 14 healthy student controls, matched for IQ with the dyslexic subjects, demonstrated a significantly better result on a test measuring ability to memorise nonsense syllables while using Piracetam as compared to placebo.
Their improvement from baseline was a 19.5% decrease in the number of trials needed to learn the nonsense syllables while using Piracetam, versus a 10.9% decrease from baseline while using placebo. P<.05. Piracetam-nootropics may increase learning and memory in healthy individuals, where they are not merely attenuating or reversing pathology, through their distinctive power to promote what has been termed "hemispheric super-connection."
The cerebral cortex in humans and animals is divided into two hemispheres- the left and right cortex. In most humans the left hemisphere (which controls the right side of the body) is the language center, as well as the dominant hemisphere. The left cortex will tend to be logical, analytical, linguistic and sequential in its information processing, while the right cortex will usually be intuitive, holistic, picture oriented and simultaneous in its information processing. Research has shown most people favor one hemisphere over the other, with the dominant cortex being more electrically active and the nondominant cortex relatively more electrically silent (when the person is being tested or asked to solve problems, or respond to information). The two cortical hemispheres are linked by a bundle of nerve "cables"; the corpus callosum and the anterior commisure. In theory these two structures should unite the function of the two hemispheres; in practice they act more like a wall separating them. This "functionally-split" neurology produces a parallel set of dichotomies in consciousness; logic vs. intuition; reason vs. emotion; analysis vs. synthesis; parts vs. whole; words vs. pictures; science vs. art and religion, etc. As noted earlier, the word "nootropic" is derived from the Greek word "nous" (the more standard philosophical spelling). Yet in the philosophy of Plato and Aristotle, "nous" did not simply mean "mind." In ancient Greek philosophy, "nous" referred to the faculty of "higher mind" or "reason," as opposed to the more concrete, sensory oriented mind which humans share even with the lower animals. And "reason" did not merely mean logic or analysis.
The Greek philosophers saw the role of philosophy to be a method of developing and perfecting nous/ reason. They understood nous/ reason to be the integrative mind, where logic works complementarily with intuition, and reason and emotion are in harmony. With a developed nous, one could clearly see and understand "the forest and the trees" simultaneously. From a modern neurological perspective it is obvious that the cerebral basis for a well-functioning nous would be the effective, complementary, simultaneous integrated function of cortical hemispheres, with neither hemisphere being automatically dominant or silent.
This in turn would require the corpus callosum and anterior commisure to optimise information flow between the two hemispheres. Research has shown the Piracetam-nootropics to facilitate such intercebral information transfer- indeed, it's part of the definition of a "nootropic drug."
Giurgea and Moyersoons reported in 1970 that Piracetam increased by 100% the transcallosal evoked responses elicited in cats by stimulation of one hemisphere and recorded from a symmetrical region of the hemisphere.
Buresova and Bures (1976) in a complex series of experiments involving monocular (one-eye) learning in rats, demonstrated that "...Piracetam enhances transcommisural encoding mechanisms... and some forms interhemispheric transfer..."
Dimond (1976, 1979) used a technique called "dichotic listening" to verify the ability of Piracetam to promote interhemispheric transfer in humans. In a dichotic listening test, different words are transmitted simultaneously into each ear by headphone. In most people the speech center is the left cortex, because the nerves from the ears cross over to the opposite side of the brain, most people will recall more of the words presented right ear than the left ear. Words received by the right ear directly reach the left cortex speech center, while words presented to the left ear must reach the left cortex speech center indirectly, by crossing the corpus callosum. Dimond's experiments with young healthy volunteers showed that Piracetam significantly improved left ear word recall, indicating Piracetam increased interhemispheric information transfer.
Okuyama and Aihara (1988) tested the effect of Aniracetam on the transcallosal response of anaesthetised rats. The transcallosal response was recorded from the surface of the frontal cortex following stimulation of the corresponding site on the opposite cortical hemisphere. Aniracetam at two different I.V. doses (10 mg and 30mg per Kg) significantly increased the amplitude of the negative wave compared to its level prior to drug, P<.01 and P<.001. The researchers stated that "the present results indicate that Aniracetam.. increased the amplitude of the negative wave, thereby facilitating interhemispheric transfer... Thus, it is considered that the functional increase in interhemispheric neurotransmission by nootropic drugs may be related to the improvement of the cognitive function."
In spite of the many and diverse neurological and psychological benefits they have shown in human, animal and cell studies, the Piracetam-nootropics are generally considered NOT to be major agonists or inhibitors of the synaptic action of most neurotransmitters. Thus, major nootropic researchers Pepeu and Spignoli (1990) state; "the pyrrolidinone derivatives [Piracetam-nootropics] show little or no affinity for CNS receptors for dopamine, glutamate, serotonin, GABA or benzodiazepine... So far, little effect of nootropic drugs has been demonstrated on brain monoamine and amino acid neurotransmitters' metabolism and release."
They also note however that "... a number of investigations on the electrophysiological actions of nootropic drugs have been carried out... Taken together, these findings indicate that the nootropic drugs of the [Piracetam-type] enhance neuronal excitability within specific neuronal pathways."
Gouliaev and Senning similarly state "... we think that the racetams exert their effect on some species [of molecule] present in the membrane of all excitable cells, i.e. the ion carriers or ion channels and that they somehow accomplish an increase in the excitatory response... It would therefore seem that the racetams act as potentiators of an already present activity (also causing the increase in glucose utilization observed), rather than possessing any activity of their own, in keeping with their very low toxicity and lack of serious side effects. The result of their action is therefore an increase in general ne sensitivity towards stimulation."
Thus the Piracetam-nootropics would NOT be prone to the (often serious effects of drugs which directly amplify or inhibit neurotransmitter c e.g. MAO inhibitors, Prozac-style "selective serotonin reuptake inhibitors, tricyclic antidepressants, amphetamines, benzodiazepines, etc.
The notable absence of biochemical, physiological, neurotogical ( chological side effects, even with high dose and/ or long terr nootropic use, is routinely attested to in the vast literature on them. Thus in their 1977 review Giurgea and Salama point out: "Piracetam active in previously described situations, is devoid of usual 're pharmacologic activities even in high doses... In normal subjects.. no side effects or 'doping' effects were ever observed. Nor did Piracetam induce any sedation, tranquillisation. locomotor stimulation or psychodysleptic symptomatology.."
Itil and co-workers.reported in 1983 that "This investigation has confirmed that [Pramiracetam] is a safe and well tolerated compound that can be given in dosages up to 1500 mg without significant side effects. In fact side effects were reported more frequently following both placebo and... phenelzine sulfate [an 'active control' drug] than following any of the four doses evaluated."
After a major 12 week study with 272 Alzheimer and stroke dementia patients, Maina and colleagues (1989) reported; "Thirty five mininor side effects were recorded in 30 patients on [Oxiracetam] and 33 unwanted efl 26 patients on placebo, but none of these was withdrawn from the study... As far as tolerability is concerned, clinical assessments and laboratory evaluations did not reveal any difference between treatment and placebo]."
Moglia and co-workers (1986) concluded from a study of 43 organic syndrome patients that "side effects during [Oxiracetam] treatment headache (3 cases), constipation (1 case), sleep disturbances (1 Side effects during placebo treatment were headache (2 case constipation (1 case). The side effects spontaneously disappears required neither medication nor treatment interruption. No significant [adverse] change in neurological and laboratory ex( lions, ECG and EEG could be detected at the end of treatment, both in the [Oxiracetam] and in the placebo groups." When side effects are occasionally reported in the clinical literature on Piracetam-nootropics. they are usually of a type to suggest slight overstimulation, mainly headaches, agitation, insomnia and irritability. Yet other studies find these same symptoms to be improved by Piracetam-nootropics when these symptoms are pre-existing in the patients. Thus Itil (1986) notes, "...[ Piracetam] showed more improvement than [Oxiracetam] in factors of paranoid delusion and agitation." Maina (1989) noted that "[Oxiracetam] does not act only by increasing arousal and alertness. If this were the case, there would probably be a worsening of the IPSC-E anxiety and tension [scores]. However, in our study there was actually a decrease in anxiety and tension." Branconnier (1983), reporting on his group's study of Pramiracetam in 32 Alzheimer patients noted that after four weeks' treatment, there was a significant decrease in anxiety-tension (P=.004) and hostility (P=.03), and a clean trend over placebo (P=.08) for Pramiracetam to improve existing sleep disturbances.
One potentially limiting factor in obtaining clinical benefit
from Piracetam-nootropics has been bought to light through the research of
Mondadori (1992) on steroid
interactions with nootropics. Mondadori has shown that either deficient or
excessive levels of adrenal steroids
can block the memory benefits of Piracetam-nootropics in animals. High doses of
either corti-costerone or aldosterone
abolish the memory enhancing benefits of Piracetam-nootropics, while giving
corticosterone or aldosterone
to rats with no adrenals restores the positive memory effects of nootropics.
Mandadori also notes that cortisol
levels are frequently elevated in Alzheimer patients, which might explain the
inconsistent results obtained with nootropics in different Alzheimer clinical
studies.
Since Piracetam-nootropics act (in part) through subtly amplifying neuronal electrical excitability, they will tend to increase the activity of other drugs that modify neural activity taken simultaneously. This in turn may increase both the positive action of the other drug, as well as possibly lead to the occasional nootropic over-stimulation effects. Thus even caffeine may be sufficiently stimulating to bring on the "nootropic over stimulation effect," especially in those very sensitive to caffeine. A key normal regulator of neuronal sensitivity is the essential mineral, Magnesium (Mg). Dietary surveys in the Western world routinely show most people to be at least marginally Mg deficient, with many getting half or less of the recommended dietary Mg intake (Wester 1987).
Thus, the occasional over stimulation seen with Piracetam-nootropics may simply evidence an undetected synaptic Mg deficiency, and Mg supplementation may provide a natural remedy to minimize such over stimulation Piracetam-nootropics have been combined in many clinical and experimental situations with other drugs, almost always with a positive, synergistic effect. Many clinical experiments have demonstrated Piracetam and Oxiracetam to synergise with anti-epileptic medications, especially carbamazepine (Tegretol). A simultaneous enhancement of the anti-epileptic drug's anti-seizure activity, combined with improvement or elimination of the memory, alertness and comprehension cognitive deficits induced 1: anti-epileptic drug, have been found in multiple studies (Chaudhry Piracetam combined with Pentoxifylline (a caffeine analogue cerebral flow enhancer) increased both "psycho-intellectual performance measures of cerebral blood flow), significantly more than place either drug alone (Parnetti 1985).
Human and animal studies have shown increased benefit from combining Piracetam with Choline. the raw material for neuronal production of be neurotransmitter Acetylcholine, as well as Phosphatidylcholine, a fluidising component of cell membranes (Ferris 1982). When Piracetam was combined with Hydergine in experiments with mice • both brain survival time and learning/ memory deficits induced poxia, it was noted that "The effect of the combination was greater than the sum of the effects of the individual agents and indicates that synergism had occurred" (Berga 1986). A 1994 report looked at the synergy between Piracetam and intensive speech therapy given to post-stroke aphasic patients; "In general, changes under [Piracetam] were 160% of the changes observed in patients receiving placebo, while getting the same intensive speech therapy" (Di 1994).
Those wishing to get the maximum benefit from Piracetam-nootropics may to include in their regimen nutrients known to enhance brain structure function in various ways.
The B-complex vitamins (including NADH), Lipoic Acid, CoQ10 (Idebenone-ed.), Magnesium and Manganese are all essential to brain ATP energy production through the glyolytic and citric acid cycles and the electron transport side chain.
DMAE (Cyprodenate or Lucidril) is an excellent Choline precursor passes the blood brain barrier better than Choline or Lecithin. Acetyl-L-carnitine (ALC) enhances the activity of the enzyme (Choline Acetyl Transferase (CAT) that combines Acetyl groups with Choline to produce Acetylcholine.
ALC also renews the structure and energy generating power of
aging neuronal mitochondria.
Phosphatidylserine
is a natural neuronal membrane component and stabilizer. Anti-oxidanants, such
as vitamins C and E, as well as Pycnogenol
or grape
seed extract, may protect polyunsaturate fat-rich neuronal and
mitochondrial membranes from the damage caused by the inevitable release of
large numbers of free radicals, generated through brain mito-chondrial energy
production.
Individual differences of action between Piracetam, Oxiracetam, Pramiracetam, and Aniracetam are often subtle, and in many studies they show similar modes of action. One intriguing benefit I have seen reported only for Pramiracetam, is its ability to increase goal directed and purposive behavior (Branconnier 1983). After trying Pramiracetam in my regimen several years ago. I did notice an increase in my tendency to quickly take care of routine household, auto and personal maintenance chores I habitually tended to ignore, avoid or postpone.
I have taken Piracetam for eight years, Pramiracetam and Aniracetam for the past two years and Oxiracetam for about 9 months. During the past year, my lifelong severe writer's block has gradually disappeared, and my writing output of the past year has exceeded that of the previous decade. Some studies on dementia comparing Piracetam and Oxiracetam (the two most nearly identical racetams). have suggested that Oxiracetam may be more effective in restoring the cognitive deficits of dementia (decreased memory, concentration and alertness), while Piracetam may be more effective at normalising the emotional problems of dementia (agitation, tension-anxiety, hostility, insomnia, uncooperativeness).
Quantitatively, Piracetam is the least potent racetam, with clinical doses typically being 2400 mg to 4800 mg per day, occasionally even 6000 mg to I0,000 mg per day.
Oxiracetam is usually given 500 mg to 2400 mg per day. Aniracetam doses are typically 750 mg to 1500mg per day, while Pramiracetam has shown benefit even at 150 mg to 500 mg per day, although 600 mg to 1500 mg per day is more typical.
Piracetam and Oxiracetam are highly water soluble (96-98%), while Aniracetam and Pramiracetam are more fat soluble. Their lipophilicity may allow for less frequent dosing (once or twice daily) with Aniracetam and Pramiracetam, compared to 3 to 4 doses a day with Piracetam and Oxiracetam.
Aniracetam is favored by the Japanese, who have contributed much research on it. It is widely used there as an agent to rapidly promote clarity of thought.
During the past 30 years, the Piracetam -nootropics have been used to treat an amazingly broad range of human ailments and conditions, either or with other drugs, with moderate to major benefit. Piracetam-nootropics have been used to treat various forms of dementia and "organic brain syndrome." They have been used successfully to treat dyslexia, epilepsy and age-associated memory impairment. Piracetam-nootropics have successfully treated post-concussional syndrome, vertigo, alcohol withdrawal, cerebrovascular insufficiency and hypoxia. They have shown benefit in normalising blood flow parameter creased platelet aggregation, increased red blood cell (RBC) deformability, decreased adherence of damaged and sickle cell RBC's dothelium (blood cell lining) and increased Prostacyclin (PG12) production and activity.
Yet the most exciting potential benefits of the racetams have yet seriously explored in clinical studies.
The racetams are cerebral homeostatic normalizers, neuroprotectants, cerebral metabolic enhancers and brain integrative agents. They enhance brain energy, especially under deficit condition: hypoxia, chemical toxicity or impaired cerebral microcirculation. They preserve, protect and enhance synaptic membrane and receptor structure and plasticity.
They enhance brain integration- horizontally, by increased coupling of the cerebral hemispheres; and vertically by enhancing cerebral connection with and tonic control of the limbic system, through nootropics effects on the hippocampus- a major link between cerebrum and system.
This vertical integration increase may help to integrate reason (cerebrum and emotion (limbic system- sometimes called the "horse brain"). The increased tonic cortico-subcortical control and regulation me prevent our limbic passions and desires from "running away with us" as in crimes of passion.
In middle aged and older individuals who do not yet suffer any specific neural malady or major mental impairment, nootropics may not only slow down or postpone entropic brain aging, but they may even reverse mild neural/ mental decline. Thus a person at 50 might be smarter, have better memory, quicker reflexes and greater vigilance and alertness than when they were 40. The racetams may literally be safe and effective pharmacologic tools to enhance, protect and optimize truly normal, fully human neuropsychological structures and function, well into old age.
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15. T. Itil et al (1986) "CNS pharmacology and clinical therapeutic effects of Oxiracetam" Clin. Neuropharmacol. 9, S70-S72.
16. G. Maina et al (1989) "Oxiracetam in the treatment of p degenerative and multi infarct dementia" Neuropsychobiol. 21. 14117. P. Mindu et al (1976) "Piracetam induced improvement of n performance" Acta Psychiat. Scanda.
18. A. Moglia et al (1986) "Activity of Oxiracetam in patients with organic brain syndrome" Clin. Neuropharmac 9, S73-S78.
19. C. Mondadori et al (1992) "Elevated corticosteroid levels block the memory improving effects of nootropics" Psychopharmac. 108, 1 1-'
20. F. Moyersoons, C. Giurgea (1974) "Protective effect of Piracetam in experimental barbiturate intoxication: EEG and behavioural studies Arch. Int. Pharmacodyn Ther 210. 38-48.
21. S. Okuyama, H. Aihara (1988) "Action of nootropic drugs on transcollosal responses of rats" Neuropharmac. 27. 67-72.
22. L. Parnetti et al (1985) "Haemorheological pattern in initial mental deterioration; Results of a long term study using Piracetam and Pe fylline" Arch Gerontol. Geriatr4, 141-55.
23. G. Pepeu. G. Spignoli (1990) "Neurochemical actions of nootropic drugs" in Advances in Neurology V51; Alzheimer’s disease. R. Wu ed. 247-52, Raven Press.
24. B. Saletu et al (1985) "..Oxiracetam in the organic brain syndrome of late life" Neuropsychobiol 13, 44-52.
25. K. Schaffler, W. Klausnitzer (1988) "..Antihypoxidotic effects of Piracetam using psychophsiological measures in healthy volunteers" Ar Forsch. Drug Res. 38, 288-91.
26. M. Tacconi, R. Wurtman (1986) "Piracetam, physiological disposition and mechanisms of action" in Advances in Neurology V43; Myocio Fahn, ed. 675-685, Raven Press.
27. P. Wester (1987) "Magnesium" Am. J. Clin. Nutr. 45, 1305-12.
28. C. Wilsher et al (1987) "Piracetam and dyslexia: Effects on reading tests" J. Clin. Psychopharmac. 7, 230-37.
The term nootropic comes from a Greek word meaning "acting on the mind". Since the invention of piracetam by UCB Laboratories in Belgium, other pharmaceutical companies have been scrambling to develop their own nootropics. Some of them being researched now include; vinpocetine, aniracetam, pramiracetam, and oxiracetam. As yet, there is no nootropic compound that id FDA approved for sale in the US, but there is plenty of motivation on the part of pharmaceutical companies to get that approval. Financial analysts expect that the US market for these cognitive enhancers will soon be in excess of $1-billion per year (Pelton, 1989).
Piracetam is very similar in molecular structure to the amino acid pyroglutamate (see Pyroglutamate). Piracetam and pyroglutamate have the same "base" chemical structure, the 2-oxo-pyrrolidine, but they differ by the side chain. Pyroglutamate is 2-oxo-pyrrolidine carboxylic acid, and piracetam is 2-oxo-pyrrolidine acetamide.
Piracetam enhances cognition under conditions of hypoxia (too little oxygen), and also enhances memory and some kinds of learning in normal humans. Outside of the US, piracetam is used to treat alcoholism, stroke, vertigo, senile dementia, sickle cell anemia, dyslexia, and numerous other health problems (Pelton, 1989).
The effect of piracetam can be increased if taken with DMAE, centrophenoxine, choline, or Hydergine. When choline and piracetam are taken together there is a synergistic effect that causes a greater improvement in memory than the sum of each when taken alone (Bartus, 1981).
We know of one person who claims she feels slightly agitated and depressed if she takes piracetam for more than a week without a choline supplement. This feeling is alleviated for her with a single dose of choline. It may be that the piracetam causes acetylcholine to be used up more quickly and that the choline helps to replace this important neurotransmitter.
Once fascinating study suggests that piracetam might increase the number of cholinergic receptors in the brain. Older mice were given piracetam for two weeks and then the density of muscarinic cholinergic receptors in their frontal cortexes was measured. The researchers found that these older mice had 30-40% higher density of these receptors than before. (Pilch, 1988). Piracetam, unlike many other drugs, appears to have a regenerative effect on the nervous system.
One theory of Alzheimer's disease is that the decline of intellectual functions is partly caused by a decreased activity of the cholinergic system in the brain caused by cell death and cell degeneration. The researchers in the above study speculated that their findings could explain how piracetam works and could also explain the finding of Bartus, et. al. regarding a profound effect of combining choline with piracetam on memory enhancement of old rats.
As mentioned previously the late drug researcher Arthur Cherkin related to us that he believed the combination of Hydergine and Piracetam potentiate each other by 5 times. This highlights the importance of adjusting the dosage when multiple substances are taken because, some of these substances will cause paradoxical effects when excessive amounts are taken.
Although piracetam is a derivative of GABA (gamma amino butyric acid, a neurotransmitter), there is no evidence that piracetam works through the GABAergic system. Some research even suggests GABA may even inhibit memory and learning (Zhang, 1989).
Precautions: Piracetam may increase the effects of certain drugs, such as amphetamines, psychotropics, and Hydergine, as stated. Adverse effects are rare but include insomnia, psychomotor agitation, nausea, gastrointestinal distress, and headaches. Piracetam has virtually no known toxicity or contraindications.
Dosage: Piracetam is supplied in 400mg or 800mg capsules or tablets. The usual dose is 2400 to 4800 mg per day in three divided doses. Some literature recommends that the first two days a high "attack" dose should be taken. We have noticed that often when people first take piracetam they do not notice any effect at all until they take a high dose (approximately 4000 to 8000mg). Thereafter, they may notice that a lower dosage is sufficient. Piracetam takes effect within 30 to 60 minutes.
Sources: Piracetam is not sold in the US. It can be purchased over the counter in Mexico or by mail form the sources listed in appendix A.
Other names include: Avigilen, Cerebroforte, Cerebrospan, Cetam, Dinagen, Encefalux, Encetrop, Euvifor, gabacet, Genogris, Memo-Puren, Nootron, Nootrop, Nootropil, Nootropyl, Normabrain, Norzetam, Pirroxil, Psycotron, Stimucortex, and UCB-6215.
1133 Piracteam Abstracts in Medline
200ish Aniracetam Abstracts in Medline
142 Oxiracetam Abstracts in Medline
75 Nefiracetam Abstracts in Medline
34 Pramiracetam Abstracts in Medline
August Krogh Institute, University of Copenhagen, Denmark.
1. The influence of acute and chronic treatment with piracetam on spatial working memory of rats was examined. A new version of an operant chamber "delayed match-to-position task" was used, in which the animals had to visit one randomly baited box out of three boxes ("choice boxes") in a front panel. Hereafter a delay period began, in which the subjects had to visit an alcove in the back panel ("reference box"). At the end of the delay the animals should return to the front panel and choose the same choice box that was baited before the delay, thereby obtaining a reward. 2. Rats were trained to a stable level of performance, measured as per cent correct responses during sessions of 20 trials. Additionally, the time spent between leaving the choice box and entering the reference box was recorded. Results were obtained from a single group of rats tested repeatedly under different experimental conditions. 3. Injections of scopolamine (0.6 mg/kg) significantly reduced the percentage of correct choices and increased the time spent to reach the reference box. The impairment of correct choices was reversed after chronic treatment with piracetam (250 mg/kg). However, the same treatment did not reverse the effect of scopolamine on the time performance. 4. Scopolamine also induced an increase of repetitive errors (a measure of perseverance), and the chronic treatment with piracetam caused full reversal of this increase. These results represent the first observation of a piracetam induced reversal of scopolamine impairments in a working memory test. 5. In normal animals not treated with scopolamine, acute injection of piracetam had no effect compared to saline injected controls, but chronic treatment with the nootropic significantly enhanced working memory performance. The drug did not affect the time used to reach the reference box.
PMID: 9533177, UI: 98194372
Pharma Division, Preclinical Research, F. Hoffman-La Roche Ltd, Basel, Switzerland.
The memory enhancing effect of the pyrrolidinone derivative aniracetam was investigated in rats trained in a delayed-response task in an 8-arm radial maze. Oral administration of aniracetam (100, 200, 400, or 800 mg kg-1) 16 h and again 1 h prior to a first trial of exposure to a given configuration of 4 baited arms resulted in a significant improvement in performance during a second trial in the maze given 3 h later in which there was access to all 8 arms but only the other 4 arms were baited. The pattern of baited arms was varied daily. The performance enhancement was greatest for the highest doses. These results extend the demonstration of the cognition enhancing effects of aniracetam to a spatial memory task in rats.
PMID: 1611039, UI: 92305255
Nootropyl (Piracetam) a drug reported to facilitate learning in animals was tested for its effect on man by administering it to normal volunteers. The subjects were given 3x4 capsules at 400 mg per day, in a double blind study. Each subject learned series of words presented as stimuli upon a memory drum. No effects were observed after 7 days but after 14 days verbal learning had significantly increased.
Publication Types:
PMID: 826948, UI: 77079535
A double-blind, intra-individual cross-over comparison of the mental performance of 18 aging, non-deteriorated individuals during two 4-week periods of piracetam (1-acetamide-2-pyrrolidone) and placebo administration was performed using conventional and computerized perceptual-motor tasks. In a majority of these tasks the subjects did significantly better when on piracetam than on placebo, a finding consistent with ratings completed by two independent observers. The findings indicate new avenues for the treatment of individuals with reduced mental performance possibly related to disturbed alertness--a neglected group of psychiatric conditions.
"
Mindus and colleagues (1976) reported the results of a double blind crossover trial with 18 healthy middle aged people (median age 56), with no evidence of somatic or mental disease, based on medical records and administration of several intelligence tests (group mean IQ; 120 plus or minus 11).
Most of the subjects were in intellectually demanding jobs, but had reported a slight reduction for some years in their capacity to retain or recall information.
After four weeks of 4.8 grams per day Piracetam, Piracetam subjects were switched to placebo for four weeks, while the original placebo group then received Piracetam for four weeks.
Results of a series of paper and pencil tests, as well as computerised tests to measure perceptual motor reactions, showed a clear benefit of Piracetam over placebo.
The three different paper and pencil tests showed superior effects on performance compared to placebo, with confidence levels of P<.001, P<.001 and P<.05. In four of the six computerised tests Piracetam showed a significant effect over placebo, with confidence levels of P<.05 for three and P<.029 for the fourth.
"
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PMID: 785952, UI: 76274634
Sixteen male dyslexic children were seen again when adults and matched with 14 student volunteers for a 21-day trial of piracetam. It was found, using a double-blind cross-over technique, that dyslexics significantly increased their verbal learning by 15.0% and students by 8.6% (over and above their placebo increase).
"A fifth test showed a clear trend in favor of Piracetam, with P<.10. Wilsher and co-workers (1979) related their results with 4.8 grams per day Piracetam in a double blind, crossover trial to study the benefits of Piracetam for dyslexic students.
Interestingly, the 14 healthy student controls, matched for IQ with the dyslexic subjects, demonstrated a significantly better result on a test measuring ability to memorise nonsense syllables while using Piracetam as compared to placebo.
Their improvement from baseline was a 19.5% decrease in the number of trials needed to learn the nonsense syllables while using Piracetam, versus a 10.9% decrease from baseline while using placebo. P<.05. Piracetam-nootropics may increase learning and memory in healthy individuals, where they are not merely attenuating or reversing pathology, through their distinctive power to promote what has been termed "hemispheric super-connection.""
Publication Types:
PMID: 116285, UI: 80057408
"Giurgea and Salama report the confirmation of Dimond/ Brouwer's work by Wedl and Suchenwirth in 1977. Wedl found significant improvement in mental performance in a group of 17 healthy young volunteers given 3.2 grams per day Piracetam for five days.""
Neuroscience Centre for Cognition and Memory, August Krogh Institute, University of Copenhagen, Denmark. GChristoff@AKI.KU.DK
Young male rats, trained in a spatial three-choice test, showed improved task acquisition after chronic treatment with piracetam (250 mg kg(-1)). After reaching a learning criterion, one group of animals was observed during Pavlovian extinction of the task skill and another group was assigned to reversal learning. The rate of extinction was slowed down in piracetam treated specimens compared to control animals. During reversal training, a new choice had to be learned while the previously acquired choice was no longer reinforced. Acquisition of the new skill was significantly impeded by piracetam in contrast to acquisition of the first skill, which was facilitated. Also during reversal learning, the piracetam treated group persevered longer than the control group in repeating the first acquired choice at the expense of learning the new choice. It is therefore suggested, that the impediment of reversal learning was caused by inhibition of extinction. In an open-field test, the time spent exploring in motion was increased by piracetam while the velocity of locomotion was unaffected by the drug. In a novelty test, piracetam increased the rate of loss of interactions with the novel object.
PMID: 9707295, UI: 98370792
Brain and Behaviour Research Group, The Open University, Milton Keynes, UK.
We investigated the effects of piracetam, a nootropic, on learning and memory formation for a passive avoidance task in day-old chicks. To test for the possible cognitive-enhancing properties of piracetam, a weak learning version of this task--whereby chicks maintain a memory to avoid pecking at a bead coated in a diluted aversant for up to 10 h--was used. Post-training (5, 30 or 60 min), but not pretraining, injections of piracetam (10 or 50 mg/kg, i.p.) increased recall for the task when the chicks were tested 24 h later. Because previous studies showed that long-term memory for the passive avoidance task is dependent upon a brain corticosteroid action, and because the efficacy of piracetam-like compounds is also modulated by corticosteroids, we tested whether the facilitating effect of piracetam was dependent upon a corticosteroid action through specific brain receptors (mineralocorticoid receptor and glucocorticoid receptor). First, increased plasma levels of corticosterone were found 5 min after piracetam injection. In addition, intracerebral administration of antagonists for each receptor type (RU28318, for mineralocorticoid receptors, and RU38486 for glucocorticoid receptors; i.c.) given before the nootropic inhibited the facilitative effect of piracetam on memory consolidation. These results give further support to a modulatory action of piracetam on the mechanisms involved in long-term memory formation through a neural action that, in this learning model, requires the activation of the two types of intracellular corticosteroid receptors.
PMID: 9749752, UI: 98420181
Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russian Federation.
Normal aging is known to deteriorate memory, spatial orientation, and perceptual recognition. Experiment 1 examined behavioral manifestations of aging by using a cross-maze exploration test in 2-, 6-, and 10-month-old hybrid mice (CBA x C57BL). A decrease in explorative patrolling and an increase in arm reentries, a latency to start and a total time of exploration were found in 10-month-old mice. In Experiment 2, administration of the cognition enhancer piracetam (2-oxo-1-pirrolidone acetamide) (400 mg/kg, IP, once a day for 10 days) enhanced arm patrolling and decreased reentries in 10-month-old mice to the level displayed by the 2-month-old animals. The results suggest that the cross-maze test may be useful for a preliminary screening of antisenescent drugs.
PMID: 8545486, UI: 96104182
Emotional stress was caused in rats by changing the location of the gate in the shuttle chamber through which training had been accomplished in the previous experiments. The procedure led to disorder of the avoidance response (AR) and increase of intertrial responses (ITR). Phenazepam (0.1 mg/kg) prevented increase in the number of ITS. Piracetam (300 mg/kg) reduced the sharp growth of ISR but, in contrast to phenazepam, it provided a higher level of AR reproduction. The ISR were greater in piracetam than in phenazepam administration. The obtained results show that the suggested model allows the difference in the effects of piracetam and phenazepam to be disclosed.
PMID: 9181869, UI: 97262764
Laboratoire de Neurobiologie des Restaurations Fonctionnelles, Universite de Provence/CNRS, UMR 6562, Neurosciences Integratives et Adaptatives, 52 Faculte des Sciences St Jerome, Marseille, France.
Immediate postlesion reorganization of the somatosensory cortical representation was examined in adult rats. Response properties of small clusters of neurons were recorded in the area of the primary somatosensory cortex (SI) devoted to the contralateral forepaw representation. Electrophysiological maps were elaborated on the basis of the sensory 'submodality' (cutaneous or noncutaneous) and the location of the peripheral receptive fields (RFs) of layer IV neurons. Recordings were made prior to, and from 1 to 12 h after, induction of a focal neurovascular lesion to the SI cortex that initially destroyed a part (8.5%) of the cutaneous representation. Moreover, the influence of an anti-ischaemic substance (piracetam) on lesion-induced changes was analysed. The main observations were: (i) a gradual outward expansion of the area of the functional lesion, which was smaller in the piracetam-treated (PT) rats than in the control, placebo-treated (PL) rats; (ii) a substantial remodelling of the spared representational zones, both in cortical sectors adjoining the site of injury and those remote from the site; (iii) a significant postlesion increase in the size of cutaneous RFs in the PT rats, but not in the PL rats; (iv) a better preservation of RF submodality and topographic organization in the PT maps than in the PL maps; and (v) a decrease in neuronal responsiveness to cutaneous stimulation which was less pronounced in the PT than in the PL rats. Our results can be ascribed to a rapid change in the balance of excitatory and inhibitory connections which leads to unmasking of subthreshold inputs converging onto cortical neurons. Our findings also indicate that acute piracetam treatment exerts a protective function on the physiological response properties of cortical neurons after focal injury.
PMID: 10457159, UI: 99388258
Healthy volunteers with a low vestibular tolerance were exposed to Coriolis acceleration. Potassium orotate, pyracetame and riboxine were used as prophylactic measures against disorders in the function of the vestibular apparatus and higher compartments of the higher nervous system. The central nervous function was assessed with respect to the spectral power of electroencephalograms, short-term memory and mental performance. Potassium orotate given at a dose of 40 mg/kg body weight/day during 12-14 days as well as pyracetame given at a dose of 30 mg/kg body weight/day during 3 or 7 days increased significantly statokinetic tolerance and produced a protective effect on the central nervous function against Coriolis acceleration.
PMID: 3784525, UI: 87062395
I.T.E.M.-LABO, Le Kremlin-Bicetre, France.
The effects of piracetam (64, 128, and 256 mg/kg PO) on the performance of a delayed alternation in a Skinner Box were investigated. Test sessions consisted of 36 trials during which animals were first presented with a single lever (left or right) followed 5, 10, or 20 s later by two levers. A press on the lever opposite to that presented previously (nonmatching to sample) was rewarded. The number of correct responses and the reaction times to the one- and two-lever presentations were recorded. All animals received all treatments in a balanced order. Aged animals showed clear deficits on all three parameters. Piracetam was without effect on the performance of young animals but dose-dependently decreased the choice reaction times (two levers) in aged animals without affecting the other two parameters. These results suggest that piracetam does not affect short-term memory but may facilitate choice behavior in aged animals.
PMID: 7862724, UI: 95166867
The study covered influence of Piracetam on occupationally important functions of memory and attention in hypertensive patients exposed to psychoemotional stress at work. The medicine appeared to improve psychic state, mental performance and the occupationally important function of memory, causing no effects on the attention. Besides hypotensive effect the medicine resulted in better clinical and physiologic parameters and increased physical performance.
PMID: 8646455, UI: 96229731
The authors' aim was to develop schemes of hypertension stage I-II treatment in subjects exposed to nervous and emotional stress at their jobs. These patients benefited from ambulatory monotherapy with obsidan or piracetam (improvement in psychic status, mental and muscular performance, in memory and attention). Reserpin worsened the patients' activity, mental performance and cognitive functions. Combination of piracetam plus reserpin promoted positive changes in psychic status, mental performance and amnestic function in stage IB-II hypertension. This combination is thought effective for inpatient treatment of hypertensive subjects exposed to psychoemotional stress.
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PMID: 9054044, UI: 97176314
It was established that propranolol in a daily dose of 2 mg/kg causes disturbance of behavior of rats with arterial hypertension in the open field, deteriorates retention of memory traces in passive avoidance paradigm, and leads to the development of depression in the test for zoosocial interrelation. Administration of nootropic piracetam (200 kg/mg/24 h). as well as the original compounds ACP-94 (20 mg/kg/24 h) and PIR-87--6-0 (50-mg/kg/24 h) facilitates the correction of negative changes in the behavior and memory of hypertensive rats.
PMID: 9324403, UI: 97381198
Ministry of Health, Bakirkoy State Hospital, Clinics of Paediatrics, Istanbul, Turkey.
To evaluate the efficacy of piracetam therapy, 76 children with breath-holding spells admitted to the Outpatient Clinic of Dicle University Medical Faculty Paediatrics Department and Bakirkoy State Hospital, Paediatrics Department between 1988 and 1990 and 1991 and 1996, respectively, were included in this placebo-controlled trial. Diagnosis of breath-holding spells was made for all cases by medical history, pediatric physical examination, electroencephalogram, and laboratory findings. Placebo or piracetam as suspension was administered to patients on a randomized basis; piracetam was administered to children in suspension 40 mg/kg/day in 2 divided doses for a period of 2 months. Of the 76 children enrolled, 39 received piracetam and 37 received placebo. Overall, control of breath-holding spells was observed in 92.3% of the patients in the group taking piracetam as compared with 29.7% in the group taking placebo (P < .05). No differences between the 2 groups in adverse events or side effects were observed. Complete blood count, biochemical profile, and urine analysis taken before and after treatment revealed no change from beginning to end and no difference between the 2 groups. It is suggested that piracetam is a safe and effective drug, with an incidence of side effects no different from that of placebo, for the treatment of breath-holding spells.
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PMID: 9492090, UI: 98151054
Research Center for Safety of Bioactive Compounds, Staraya Kupavna, Moscow Region.
[Record supplied by publisher]
The effect of new agent Vp (9-butylamine-3,3-dimethyl-3,4-dihydroacridine-1(2H) hydrochloride) on lifetime of isolated mechanoreceptive crayfish neurons was evaluated by the duration of its impulse activity. Vp significantly and dose-dependently prolonged the lifetime of both spontaneously degrading neurons and neurons degrading under conditions of inhibition of various stages of the energy metabolism: glycolysis and oxidative phosphorylation. The effect of Vp in a concentration of 10(-7) M surpassed that of amiridine. Piracetam also prolonged the lifetime of spontaneously degrading neurons, but only in very high concentration (10(-2) M). It is concluded that Vp possesses a neuroprotective activity.
PMID: 10977921
Other Formats:
J Ethnopharmacol 2000 Sep 1;72(1-2):119-128
Smolensk Medical Academy, Russia.
A craniocerebral trauma was modelled in experiments on one-month-old rats. Oxidative phosphorylation in the brain mitochondria was studied by polarography 1, 4, 7 days and 4 weeks after the trauma. In the posttraumatic period the animals received piracetam (1 g/kg), picamilon (500 mg/kg), pyriditol (100 mg/kg), pantogam (160 mg/kg), ACTH (5-10) (0.1 mg/kg), nooglutyl (25 mg/kg), and GVS (0.5 mg/kg). It was found that piracetam, picamilon, and nooglutyl have a protective effect on the function of the brain mitochondria during the course of a craniocerebral trauma. Nooglutyl surpasses all the other drugs in its influence on the effectiveness of oxidative phosphorylation of mitochondria in immature rats in the posttraumatic period.
PMID: 9621180, UI: 98284200
Kliniki Neurotraumatologii Instytutu Neurologii Collegium Medicum UJ.
A group of 100 patients treated immediately following a cranio-cerebral injury was analyzed. The patients, administered piracetam either in an intravenous infusion (GCS 3-8) or orally (GCS above 9), were divided into groups depending on the dose and clinical status. Piracetam participates in the activity of the majority of neurotransmitters, increases glucose and oxygen consumption in the ischaemic nervous tissue and increases blood flow through cerebral terminal vessels. In cranio-cerebral injuries, piracetam is employed to achieve cytoprotection and improve cerebral blood flow. In patients with neurological deterioration following the administration of 6-10 mg/day, no good results were obtained. A dose of 24-30 mg/day had a significant positive effect on therapeutic results providing certain conditions were met, such as ensuring proper partial oxygen pressure (oxygen therapy) and proper blood glucose levels. The use of piracetam is justified immediately after an injury; after the discharge oral piracetam therapy is recommended.
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PMID: 10463232, UI: 99392528
College of Pharmacy, Chungnam National University, Taejon, South Korea. Leesc@hanbat.chungnam.ac.kr
Effects of single and repeated administration of red ginseng total saponins (ROTS) and nootropic drugs were examined on impairment of acquisition induced by single oral administration of 3 g/kg ethanol (EtOH) in a step through test. The inhibitory effect of EtOH on acquisition was significantly reduced following single or repeated RGTS administration. The nootropic drugs, piracetam and N-methyl-D-glucamine, given orally significantly reduced impairment of acquisition induced by EtOH. On the other hand, the inhibitory effect of repeated RGTS on the EtOH-induced amnesia was blocked by the pretreatment of alpha-methyl-p-tyrosine (alpha-MT), an inhibitor of catecholamine synthesis, in a dose-dependent manner but not p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, whereas the inhibitory effect of repeated N-methyl-D-glucamine on the EtOH-induced amnesia was blocked neither by alpha-MT nor PCPA. These results suggest that repeated RGTS and N-methyl-D-glucamine ameliorate the impairing effect of EtOH on acquisition, and the effect of RGTS on EtOH-induced amnesia is dependent on the catecholaminergic but not serotonergic neuronal activity, while RGTS and N-methyl-D-glucamine seem to have a different mechanism on EtOH-induced amnesia.
PMID: 10661877, UI: 20125519
Department of Anatomy, Porto Medical School, Alameda do Prof. Hernani Monteiro, Portugal.
Chronic alcohol consumption causes a depletion of the cholinergic fiber network in the rat hippocampal formation, which is not ameliorated by alcohol withdrawal. Following withdrawal from alcohol, there is a further loss of intrinsic hippocampal cholinergic neurons. In this study, we investigated whether treatment with putative neuroprotective agents during the entire withdrawal period would have beneficial effects upon the hippocampal cholinergic innervation. Adult male rats were alcohol-fed for 6 months and subsequently withdrawn from alcohol for 6 months. Some animals were treated with either ganglioside GM1 (35 mg/kg body weight s.c.), vehicle (saline s.c.), or piracetam (800 mg/kg body weight p.o.) for the entire withdrawal period. Choline acetyltransferase (ChAT) immunoreactive (IR) fibers and neurons were analyzed quantitatively in all four animal groups. There were no significant differences in the density of the ChAT-IR hippocampal fiber network when the pure withdrawal and withdrawal + vehicle groups were compared to the withdrawal + GM1 or withdrawal + piracetam groups. In contrast, the number of ChAT-IR interneurons in the hippocampal formation was higher in the withdrawal + GM1 or withdrawal + piracetam groups than in the pure withdrawal and withdrawal + vehicle groups. These results indicate that, in the doses used, neither neuroprotective agent had an effect upon the extrinsic cholinergic innervation, but they had a beneficial effect upon the hippocampal intrinsic cholinergic system.
PMID: 10487390, UI: 99415331
Department of Anatomy, Porto Medical School, Portugal.
In previous studies we have demonstrated that prolonged ethanol consumption induced hippocampal neuronal loss. In addition, we have shown that withdrawal after chronic alcohol intake augmented such degenerative activity leading to increased neuronal death in all subregions of the hippocampal formation but in the CA3 field. In an attempt to reverse this situation, we tested, during the withdrawal period, the effects of piracetam (2-oxo-1-pyrrolidine acetamide), a cyclic derivative of gamma-aminobutyric acid, as there is previous evidence that it might act as a neuronoprotective agent. The total number of dentate granule, hilar, and CA3 and CA1 pyramidal cells of the hippocampal formation were estimated using unbiased stereological methods. We found out that in animals treated with piracetam the numbers of dentate granule, hilar, and CA1 pyramidal cells were significantly higher than in pure withdrawn animals, and did not differ from those of alcohol-treated rats that did not undergo withdrawal. These data suggest that piracetam treatment impedes, during withdrawal, the pursuing of neuronal degeneration.
PMID: 7639963, UI: 95367208
Piracetam, 1-pyrrolidone acetamid, was tested in 40 chronic alcoholics with a more or less marked psycho-organic syndrome by means of psychological tests. It was a double-blind-cross-over study. Statistical analysis of the results showed that Piracetam improves the energo-functional capacity of the cortex i.e. the basal functions of the cortical cells such as activating capacity, vital dynamic, flexibility, intellectual reactivity and stress tolerance. Apart from the overall improvement we also observed an improvement of specific cerebral performances which is however unimportant in comparison with the greneralized effect.
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PMID: 775275, UI: 76195721
Department of Otorhinolaryngology, University of Amsterdam, The Netherlands.
Vertigo is a sensation of altered orientation in space and may be defined as an illusion of movement. It is a subjective symptom and therefore difficult to assess. Examination and diagnosis remain difficult. Although treatment should be directed at the underlying cause or disorder, the origin of vertigo is frequently unknown or untreatable. Pharmacotherapy is required for symptomatic treatment. Piracetam has been shown to be effective in vertigo of both central and peripheral origin. It is thought to act on vestibular and oculomotor nuclei in the brain stem and thus on the central control of balance enhancing mechanisms of compensation and habituation. This review of double-blind trials shows that piracetam alleviates vertigo after head injury, vertigo of central origin as, for example, in vertebrobasilar insufficiency and in peripheral vestibular disorders, especially in middle-aged and elderly subjects. Piracetam decreases the frequency but probably not the severity of exacerbations in patients with chronic or recurrent vertigo. The usual dosage of piracetam in vertigo is 2.4-4.8 g daily. Tolerability of piracetam is good and adverse effects have been mild and infrequent.
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PMID: 10338110, UI: 99268432
Servicio de O.R.L. Hospital Dr. Peset-S.V.S. Valencia.
From the age of sixty, vertigo is mainly due to vertebro-basilar insufficiency. It has been described that the association of Dihydroergocristine-Piracetam (D-P) is a useful treatment for vertebro-basilar insufficiency. That is why we have designed a comparative study between D-P an a Placebo, so that to prove if this association can be usefull in the treatment of vertigo occasioned by cerebrovascular insufficiency. Fifty patients complaining of vertigo were included in the study after an untreated term. 19 received a daily capsule of Placebo, and the other 31, treated with D-P, were divided in two groups: 16 patients received a dose of 3 mg Dihydroergocristine + 1.6 g Piracetam every 12 hours per os; and 15 other were treated with 1.5 mg Dihydroergocristine + 0.8 g Piracetam every 8 hours during 90 days. The patients were evaluated at the beginning of the study and 90 days later, with anamnesis and vestibular tests. In the last consultation the patients autoevaluated themselves the effect and the tolerance to the drugs received. In the Placebo group it was observed an improvement or disappearance of vertiginous symptoms in the 68.5% of the cases, while with D-P was 93.7% at the dose of 3 mg Dihydroergocristine + 1.6 g Piracetam each 12 hours and 100% with the dose 1.5 mg Dihydroergocristine + 0.8 g Piracetam each 8 hours. None of the treated patients with D-P worsened their symptoms. We observe a considerable decrease in the number of patients with vegetative symptoms in the group treated with D-P related to the Placebo group, though the symptoms persisted more time in the group treated with D-P that in the Placebo group. The group treated with D-P get a higher percentage of improvements and disappearance of auditive and cervical symptoms that the groups treated with Placebo. In the vestibulo-spinal and cerebellous tests it was observed a better improvement with D-P at the dose of 1.5 mg of Dihydroergocristine + 0.8 g Piracetam each hours compared with the other two groups. It can be concluded that the association D-P is an effective treatment for vertigo, getting also a higher normalization of the vestibular tests than Placebo.
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PMID: 10394686, UI: 99322990
Max-Planck-Institute for Neurological Research, Cologne, Germany. josef.kessler@pet.mpin-koeln.mpg.de
BACKGROUND AND PURPOSE: In a prospective, double-blind, placebo-controlled study, it was investigated whether piracetam improves language recovery in poststroke aphasia assessed by neuropsychological tests and activation PET measurement of cerebral blood flow. METHODS: Twenty-four stroke patients with aphasia were randomly allocated to 2 groups: 12 patients received 2400 mg piracetam twice daily, 12 placebo. Before and at the end of the 6-week treatment period in which both groups received intensive speech therapy, the patients were examined neuropsychologically and studied with H(2)(15)O PET at rest and during activation with a word-repetition task. Blood flow was analyzed in 14 language-activated brain regions defined on reconstructed surface views from MRI coregistered to the PET images. RESULTS: Before treatment, both groups were comparable with respect to performance in language tasks and to type and severity of aphasia. In the piracetam group, increase of activation effect was significantly higher (P:<0.05) in the left transverse temporal gyrus, left triangular part of inferior frontal gyrus, and left posterior superior temporal gyrus after the treatment period compared with the initial measures. The placebo group showed an increase of activation effect only in the left vocalization area. In the test battery, the piracetam group improved in 6 language functions, the placebo group only in 3 subtests. CONCLUSIONS: Piracetam as an adjuvant to speech therapy improves recovery of various language functions, and this effect is accompanied by a significant increase of task-related flow activation in eloquent areas of the left hemisphere.
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PMID: 10978039, UI: 20433490
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Bull Exp Biol Med 2000 Apr 1;129(4):430-433
Neurocybernetics Institute, Rostov State University, Rostov-on-Don, 344090, Russia. mam@krink.rnd.runnet.ru.
Adaptive effects of delta-sleep inducing peptide (DSIP, 12 microgram/100 g body weight, single intraperitoneal injection) and piracetam (3 mg/100 g body weight, daily intraperitoneal injection for 3 days) are manifested via differential changes in neurotransmitter amino acids (GABA, glutamate, aspartate), modulation of transport ATPase activity, and decreased accumulation of lipid peroxidation products (conjugated dienes, malonic dialdehyde, Schiff bases) in various fractions of neuronal membranes (myelin, synaptic and mitochondrial membranes) in the sensomotor cortex of rat brain. Under hyperbaric oxygenation (0.3 MPa for 2 h), the combination of DSIP and piracetam enhanced the protective effect of each compound.
PMID: 10395980, UI: 99327177
August Krogh Institute, University of Copenhagen, Denmark.
1. The influence of acute and chronic treatment with piracetam on spatial working memory of rats was examined. A new version of an operant chamber "delayed match-to-position task" was used, in which the animals had to visit one randomly baited box out of three boxes ("choice boxes") in a front panel. Hereafter a delay period began, in which the subjects had to visit an alcove in the back panel ("reference box"). At the end of the delay the animals should return to the front panel and choose the same choice box that was baited before the delay, thereby obtaining a reward. 2. Rats were trained to a stable level of performance, measured as per cent correct responses during sessions of 20 trials. Additionally, the time spent between leaving the choice box and entering the reference box was recorded. Results were obtained from a single group of rats tested repeatedly under different experimental conditions. 3. Injections of scopolamine (0.6 mg/kg) significantly reduced the percentage of correct choices and increased the time spent to reach the reference box. The impairment of correct choices was reversed after chronic treatment with piracetam (250 mg/kg). However, the same treatment did not reverse the effect of scopolamine on the time performance. 4. Scopolamine also induced an increase of repetitive errors (a measure of perseverance), and the chronic treatment with piracetam caused full reversal of this increase. These results represent the first observation of a piracetam induced reversal of scopolamine impairments in a working memory test. 5. In normal animals not treated with scopolamine, acute injection of piracetam had no effect compared to saline injected controls, but chronic treatment with the nootropic significantly enhanced working memory performance. The drug did not affect the time used to reach the reference box.
PMID: 9533177, UI: 98194372
Max-Planck-Institute for Neurological Research, Cologne, Germany. josef.kessler@pet.mpin-koeln.mpg.de
BACKGROUND AND PURPOSE: In a prospective, double-blind, placebo-controlled study, it was investigated whether piracetam improves language recovery in poststroke aphasia assessed by neuropsychological tests and activation PET measurement of cerebral blood flow. METHODS: Twenty-four stroke patients with aphasia were randomly allocated to 2 groups: 12 patients received 2400 mg piracetam twice daily, 12 placebo. Before and at the end of the 6-week treatment period in which both groups received intensive speech therapy, the patients were examined neuropsychologically and studied with H(2)(15)O PET at rest and during activation with a word-repetition task. Blood flow was analyzed in 14 language-activated brain regions defined on reconstructed surface views from MRI coregistered to the PET images. RESULTS: Before treatment, both groups were comparable with respect to performance in language tasks and to type and severity of aphasia. In the piracetam group, increase of activation effect was significantly higher (P:<0.05) in the left transverse temporal gyrus, left triangular part of inferior frontal gyrus, and left posterior superior temporal gyrus after the treatment period compared with the initial measures. The placebo group showed an increase of activation effect only in the left vocalization area. In the test battery, the piracetam group improved in 6 language functions, the placebo group only in 3 subtests. CONCLUSIONS: Piracetam as an adjuvant to speech therapy improves recovery of various language functions, and this effect is accompanied by a significant increase of task-related flow activation in eloquent areas of the left hemisphere.
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PMID: 10978039, UI: 20433490
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Bull Exp Biol Med 2000 Apr 1;129(4):430-433
Department of Psychopharmacology, Central Institute of Mental Health Mannheim, Germany.
In order to test the hypothesis that piracetam improves cognitive functions by restoring biochemical deficits of the aging brain, we investigated the effects of piracetam treatment (300 mg/kg daily for 6 weeks) on the active avoidance performance of young and aged rats. After testing, the rats were killed and membrane fluidity and NMDA as well muscarinic cholinergic receptor densities were determined in the frontal cortex, the hippocampus, the striatum, as well as the cerebellum. Piracetam treatment improved active avoidance learning in the aged rats only and elevated membrane fluidity in all brain regions except the cerebellum in the aged animals. Moreover, we observed a positive effect of piracetam treatment on NMDA receptor density in the hippocampus and on muscarinic cholinergic receptor densities in the frontal cortex and the striatum and to a lesser extent in the hippocampus. Again, these effects were only observed in aged animals. Discrimination analysis indicated that piracetam effects on membrane fluidity in the frontal cortex, the hippocampus, and the striatum and its effects on NMDA densities in the hippocampus might be involved in its positive effects on cognitive performance.
PMID: 10338103, UI: 99268425
Biull Eksp Biol Med 1992 Feb;113(2):149-50
In vitro comparative studies of effects of amiridin (9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopentane (b) choline monohydrate hydrochloride) and tacrine physostigmine and piracetam on monoamine oxidase A (MAO-A) and B (MAO-B) activity in the rat brain were carried out. Piracetam (1 x 10(-4)-1 x 10(-3) M) dose-dependently increased MAO-A and MAO-B activity. At all concentrations used (1 x 10(-7)-5 x 10(-4) M) physostigmine had no effect on MAO-A and MAO-B activity. Amiridin was found to inhibit MAO-B activity at 5 x 10(-4) M concentration only. Tacrine inhibited MAO-A activity at 5 x 10(-4) M concentration. The therapeutical effects of amiridin and tacrine in treatment of Alzheimer disease were not related to their action on MAO-A and -B activity.
PMID: 1611059, UI: 92305284
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Chung Kuo Yao Li Hsueh Pao 1992 Jan;13(1):48-50
Department of Pharmacology, Suzhou Medical College, China.
Piracetam, ig 600 mg.kg-1.d-1 for 30 d, caused a 20% decrease in the activity of Na(+)-K(+)-ATPase and monoamine oxidase (MAO) in vivo. In vitro, it presented an inhibitory effect on MAO, but had no direct effect on Na(+)-K(+)-ATPase at a concentration of 100 mmol.L-1. Piracetam had a potential action in scavenging free radicals. This action may be related to its clinical effects on amnesia and Alzheimer's disease.
PMID: 1318632, UI: 92295874
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Farmakol Toksikol 1988 May-Jun;51(3):16-8
In vitro studies of effects of some nootropic drugs (centrophenoxine, piracetam and aniracetam) on monoamine oxidase (MAO) activity in the rat striatum and hypothalamus, using tyramine, serotonin and beta-phenylethylamine as substrates, were carried out. At all concentrations used (5.10(-5)-1.10(-3) M) centrophenoxine inhibited total MAO, MAO A and MAO B in both brain structures. Piracetam activated striatal and hypothalamic total MAO, hypothalamic MAO A and MAO B but exerted a pronounced inhibitory effect on MAO A and MAO B activity in the striatum. Aniracetam inhibited total MAO and MAO A in both brain structures but activated striatal and hypothalamic MAO B. The different effects of centrophenoxine, piracetam and aniracetam on MAO activity in the brain structures support the view for the independent mode of action of nootropic drugs in spite of their similar molecular and metabolic activity.
PMID: 3137089, UI: 88312947
Department of Neurology, University Hospital, Ghent, Belgium.
Recent post-marketing surveillance reports have confirmed the benign safety profile and lack of organ toxicity shown by piracetam during its 25 years of clinical usage. Tolerance has proved equally good with the more recent use of larger doses (up to 24 g/day) for the long-term control of cortical myoclonus and when given intravenously to patients with acute stroke. This paper provides a brief review of these findings and records the safety of piracetam as found in the Piracetam in Acute Stroke Study (PASS), a randomized multicenter placebo-controlled study in 927 patients with acute ischemic stroke. Patients receive one intravenous bolus injection of placebo or 12 g piracetam, piracetam 12 g daily for 4 weeks and maintenance treatment for 8 weeks. The major results have been reported (De Deyn et al., Stroke 28 [1997] 2347-2352). Safety was assessed taking into account adverse events including abnormal laboratory test results and mortality. Death within 12 weeks occurred more frequently in the piracetam group but the difference from placebo was not significant. Of many potential risk, prognostic and treatment-related factors examined by logistic regression, 6 contributed significantly to death of which the most important were initial severity of stroke and age. Neither treatment nor any treatment-related factor contributed significantly to death. Adverse events were similar in frequency, type and severity in piracetam and placebo groups. Events of cerebral, non-cerebral and uncertain origin likewise occurred with similar frequency. Few patients discontinued because of adverse events. There was no difference between treatments in the frequency of events associated with bleeding, including hemorrhagic transformation of infarction. An important finding was that, of 31 patients with primary hemorrhagic stroke enrolled, 3 piracetam-treated patients died compared with 6 on placebo. The results suggest that piracetam in high dosage may be given to patients with acute stroke without significant adverse effects.
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PMID: 10338106, UI: 99268428
Giurgea and Moyersoons reported in 1970 that Piracetam increased by 100% the transcallosal evoked responses elicited in cats by stimulation of one hemisphere and recorded from a symmetrical region of the hemisphere.
Dimond (1976, 1979) used a technique called "dichotic listening" to verify the ability of Piracetam to promote interhemispheric transfer in humans. In a dichotic listening test, different words are transmitted simultaneously into each ear by headphone. In most people the speech center is the left cortex, because the nerves from the ears cross over to the opposite side of the brain, most people will recall more of the words presented right ear than the left ear. Words received by the right ear directly reach the left cortex speech center, while words presented to the left ear must reach the left cortex speech center indirectly, by crossing the corpus callosum. Dimond's experiments with young healthy volunteers showed that Piracetam significantly improved left ear word recall, indicating Piracetam increased interhemispheric information transfer.
Okuyama and Aihara (1988) tested the effect of Aniracetam on the transcallosal response of anaesthetised rats. The transcallosal response was recorded from the surface of the frontal cortex following stimulation of the corresponding site on the opposite cortical hemisphere. Aniracetam at two different I.V. doses (10 mg and 30mg per Kg) significantly increased the amplitude of the negative wave compared to its level prior to drug, P<.01 and P<.001. The researchers stated that "the present results indicate that Aniracetam.. increased the amplitude of the negative wave, thereby facilitating interhemispheric transfer... Thus, it is considered that the functional increase in interhemispheric neurotransmission by nootropic drugs may be related to the improvement of the cognitive function."
The effect of Piracetam (UCB 6215, 2-pyrrolidoneacetamide) on learning mediated by transcommissural information flow was studied in hooded rats. Acquisition of monocular pattern discrimination was faster in drug-treated rats (100 mg/kg, 30 min before training) than in untreated controls. Subsequent relearning with one hemisphere functionally eliminated by cortical spreading depression showed that the strength of the primary engram formed under Piracetam in the hemisphere contralateral to the trained eye remained unaffected but that the secondary trace (in the ipsilateral hemisphere) was considerably improved and almost equalled the primary one (savings increased from 20-30% to 50-60%). Learning with uncrossed optic fibers was unaffected by the drug. Interhemispheric transfer of lateralized visual engrams acquired during functional hemidecortication was facilitated by Piracetam administration preceding the five transfer trials performed with the untrained eye open (imperative transfer). Piracetam was ineffective when the trained eye was open during transfer trials (facultative transfer). After a visual engram had been lateralized by 5 days of monocular overtraining, Piracetam facilitated formation of the secondary engram induced by 3 interocular transfer trials. It is concluded that Piracetam enhances transcommissural encoding mechanisms activated in the initial stage of monocular learning and in some forms of interhemispheric transfer, but does not affect the transcommissural readout. This effect is interpreted as a special case of the Piracetam-induced facilitation of the phylogenetically old mechanisms of redundant information storage which improve liminal or subnormal learning.
PMID: 1257371, UI: 76152798
Research Laboratories, Yoshitomi Pharmaceutical Industries, Fukuoka, Japan.
The transcallosal response in aged rats was recorded and its susceptibility to certain nootropic drugs was compared with adult animals, under urethane-anesthesia. The transcallosal response in 24-month old rats was significantly reduced in the amplitude of both positive and negative waves, as compared with 5-month old animals. In adult rats, intravenous administration of 100 mg/kg of calcium hopantenate augmented the amplitude of both the positive and the negative waves. Intraperitoneal administration of 300 mg/kg of calcium hopantenate or 10-100 mg/kg of aniracetam increased the amplitude of the negative wave by 20-30% above the control level but had no effect on the positive one. In aged rats, these drugs, given intraperitoneally, also increased the negative wave without affecting the positive one and the degree of augmentation was more prominent; both drugs increased the amplitude of the negative wave by about 190% of the control. These results suggest that the susceptibility to the nootropic drugs became even more striking in older animals, the function in the brain of which are reduced by the natural ageing process.
PMID: 1436389, UI: 93063703
The KEY Institute for Brain-Mind Research, University Hospital of Psychiatry, Zurich, Switzerland.
Global complexity of 47-channel resting electroencephalogram (EEG) of healthy young volunteers was studied after intake of a single dose of a nootropic drug (piracetam, Nootropil UCB Pharma) in 12 healthy volunteers. Four treatment levels were used: 2.4, 4.8, 9.6 g piracetam and placebo. Brain electric activity was assessed through Global Dimensional Complexity and Global Omega-Complexity as quantitative measures of the complexity of the trajectory of multichannel EEG in state space. After oral ingestion (1-1.5 h), both measures showed significant decreases from placebo to 2.4 g piracetam. In addition, Global Dimensional Complexity showed a significant return to placebo values at 9.6 g piracetam. The results indicate that a single dose of piracetam dose-dependently affects the spontaneous EEG in normal volunteers, showing effects at the lowest treatment level. The decreased EEG complexity is interpreted as increased cooperativity of brain functional processes.
PMID: 10555876, UI: 20022802
Bristol-Myers Squibb Pharmaceutical Research Institute, Neuroscience Drug Discovery, Department of Electrophysiology, Wallingford, Connecticut, USA. KinneyG@bms.com
Synchronous hippocampal electroencephalographic activity occurring in a frequency range of 3 to12 Hz (i.e., hippocampal theta rhythm) has been associated with mnemonic processes in vivo. However, this link is tenuous and theta rhythm may be secondary to processes that underlie mnemonic function. If theta rhythm is associated with mnemonic or cognitive function, cognition-enhancing drugs should enhance theta rhythm regardless of their primary biological target. In the current study, we evaluated several drugs that were shown to have cognition-enhancing properties in preclinical behavioral models and that vary with respect to their primary biological target: 1) the nootropic piracetam (250 and 500 mg/kg); 2) the small-conductance calcium-activated potassium-channel blocker apamin (0.1 and 0.4 mg/kg); and 3) the acetylcholinesterase inhibitor donepezil (0.1-10.0 mg/kg). All of the cognition-enhancing drugs produced dose-dependent increases in hippocampal theta rhythm amplitude elicited by stimulation of the brainstem reticular formation at doses that did not affect peak theta frequency in the urethane-anesthetized rat. These increases were reversed by the muscarinic receptor antagonist scopolamine, suggesting a common final cholinergic action of these compounds. The use-dependent N-methyl-D-aspartate antagonist dizocilipine maleate and scopolamine reduced theta amplitude (both) and frequency (dizocilipine maleate only). These data demonstrate that hippocampal theta rhythm is sensitive to cognition-modulating compounds, suggesting that theta rhythm may be closely associated with cognitive function.
PMID: 10490892, UI: 99421890
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
Electrical stimulation patterned after the hippocampal theta rhythm produces a robust and stable long-term potentiation (LTP) effect. Pharmacological manipulations were used in the present studies in an effort to relate characteristics of the responses occurring during theta stimulation to the magnitude of potentiation which follows it. Comparisons were made using five or ten bursts of stimulation which respectively induce sub-maximal or near maximal degrees of LTP. DPCPX, a drug that increases release by blocking adenosine A1 receptors, was used to enhance the depolarization produced by individual theta bursts. This resulted in a marked increase in the amount of stable LTP induced by five theta bursts but did not affect that resulting from ten bursts. This finding suggested that depolarization occurring during a burst response influences per burst potentiation but not the ceiling on maximum LTP. Aniracetam, a nootropic drug that enhances responses via an action on glutamate (AMPA) receptors, was used to test this conclusion. Like DPCPX, aniracetam increased the size of the burst response and enhanced the degree of LTP caused by five but not ten theta bursts. Forskolin, an activator of adenylate cyclase, was used to test the effects of blocking the hyperpolarization normally present between theta bursts on the induction of LTP. The drug augmented the degree of LTP resulting from five theta bursts and, in contrast to DPCPX and aniracetam, nearly doubled that obtained with ten bursts. Thus the drug affected both per burst potentiation and the ceiling on LTP. These results are discussed in terms of an hypothesis in which the magnitude of NMDA receptor mediated currents affects the degree of potentiation produced by individual theta bursts while the duration of the currents is related to the limit on the maximum LTP induced by a series of bursts. The possible implications of the findings for learning are also considered.
PMID: 1486479, UI: 93137006
Research Center, Taisho Pharmaceutical Co. Ltd, Saitama, Japan.
The effects of nootropic drugs and related compounds on transcallosal responses were examined in urethane-anesthetized rats. The transcallosal response was recorded from the surface of the anterior neocortex following electrical stimulation of the contralateral corpus callosum. The transcallosal response consisted of a biphasic positive-negative waveform. Hopantenate increased the amplitude of the positive- and negative-waves, without affecting the latency. Aniracetam, idebenone, bifemelane hydrochloride, TRH and meclofenoxate increased the amplitude of the negative-wave, without affecting the latencies. Vinpocetine and eburunamonine had no effect on the transcallosal response. Muscimol, amino-oxyacetic acid, diazepam and pentobarbital increased the amplitude of the positive-wave and decreased the amplitude of the negative-wave, without affecting the latencies. Bicuculline and picrotoxin increased the amplitude of the negative-wave, without affecting the latencies. Physostigmine decreased the amplitude of the negative-wave, without affecting the latency. Atropine was without effect. The pharmacological nature of the transcallosal response is discussed, based on findings with 16 different pharmacological agents.
PMID: 3352867, UI: 88175422
It has been established in mouse experiments that potassium orotate (100 mg/kg) and piracetam (500 mg/kg) given in chronic oral doses have an antidepressant activity according to the "behavioral despair" test. It has been demonstrated that antidepressant activity of potassium orotate (20 and 50 mg/kg) and piracetam (50 and 100 mg/kg) is associated with a psychostimulant effect.
PMID: 3996568, UI: 85204319
In the social interaction test of anxiety Piracetam (100 mg/kg) had an anxiolytic profile very similar to that seen after 5 days of administration of chlordiazepoxide (5 mg/kg). Piracetam (50-300 mg/kg) produced no signs of sedation and it was therefore suggested that it might be a non-sedative anxiolytic drug. Piracetam (100 mg/kg) produced significantly higher cortical concentrations of 5-hydroxytryptamine and lower concentrations of 5-hydroxyindoleacetic acid, indicating a reduced 5-HT turnover. There were no drug-induced changes in noradrenaline or dopamine in any brain region, either with or without pretreatment with alpha-methylparatyrosine. The cortical concentrations of 7 amino acids were measured and were unchanged by treatment with Piracetam.
PMID: 95599, UI: 82168483
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
Electrical stimulation patterned after the hippocampal theta rhythm produces a robust and stable long-term potentiation (LTP) effect. Pharmacological manipulations were used in the present studies in an effort to relate characteristics of the responses occurring during theta stimulation to the magnitude of potentiation which follows it. Comparisons were made using five or ten bursts of stimulation which respectively induce sub-maximal or near maximal degrees of LTP. DPCPX, a drug that increases release by blocking adenosine A1 receptors, was used to enhance the depolarization produced by individual theta bursts. This resulted in a marked increase in the amount of stable LTP induced by five theta bursts but did not affect that resulting from ten bursts. This finding suggested that depolarization occurring during a burst response influences per burst potentiation but not the ceiling on maximum LTP. Aniracetam, a nootropic drug that enhances responses via an action on glutamate (AMPA) receptors, was used to test this conclusion. Like DPCPX, aniracetam increased the size of the burst response and enhanced the degree of LTP caused by five but not ten theta bursts. Forskolin, an activator of adenylate cyclase, was used to test the effects of blocking the hyperpolarization normally present between theta bursts on the induction of LTP. The drug augmented the degree of LTP resulting from five theta bursts and, in contrast to DPCPX and aniracetam, nearly doubled that obtained with ten bursts. Thus the drug affected both per burst potentiation and the ceiling on LTP. These results are discussed in terms of an hypothesis in which the magnitude of NMDA receptor mediated currents affects the degree of potentiation produced by individual theta bursts while the duration of the currents is related to the limit on the maximum LTP induced by a series of bursts. The possible implications of the findings for learning are also considered.
PMID: 1486479, UI: 93137006
Department of Physiology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. tomo@med.kobe-u.ac.jp
Nefiracetam, a nootropic agent, enhanced the slope of field excitatory postsynaptic potentials in the CA1 region of rat hippocampal slices to about 170% of basal levels, being evident still at 4-h washing-out of the drug. A similar sustained enhancement (>/=16 h after i.m. injection with nefiracetam) was observed in the population spikes recorded from the granular cell layer of the intact mouse hippocampus. Saturation of the enhancement in the synaptic strength occluded potentiation obtained with long-term potentiation (LTP) induced by high-frequency (tetanic) stimulation, and vice versa. Interestingly, the facilitatory action of nefiracetam was blocked by either the nicotinic acetylcholine (ACh) receptor antagonists, alpha-bungarotoxin and mecamylamine, or the selective protein kinase C (PKC) inhibitor, GF109203X, but in contrast, it was not affected by D-2-amino-5-phosphonovaleric acid (APV), a selective N-methyl-D-aspartate (NMDA) receptor antagonist. The results of the present study suggest that nefiracetam, whereas the action is independent of NMDA receptors, induces an 'LTP-like' facilitation of hippocampal synaptic transmission as a consequence of modulation of nicotinic ACh receptors and PKC. This may represent a likely mechanism underlying the cognition-enhancing actions of nefiracetam. Copyright 1999 Elsevier Science B.V.
PMID: 10224305, UI: 99242390
Aniracetam, 1-p-anisoyl-2-pyrrolidinone, is known to be a nootropic or cognitive activator. Aniracetam protects against memory and learning deficits without causing effects on motor function and the autonomic nervous system. A drug dependence study on aniracetam utilizing the intragastric route of administration was performed in male cynomolgus monkeys. The behavioral observation test after acute administration revealed that aniracetam at the dose of 25-400 mg/kg did not change the gross behavior. In the self-administration initiation test, animals were exposed to two or three unit doses of aniracetam and references for a total available period of 7 weeks. Aniracetam at the dose of 25, 50 and 75 mg/kg/injection did not initiate self-administration in the respective group of 4, 4 and 2 animals. In the study with d-methamphetamine hydrochloride at the dose of 0.1 mg/kg/injection, 1 out of 4 animals started to consistently self-administer the drug. Self-administration of cocaine hydrochloride at the dose of 10 mg/kg/injection was confirmed in 3 out of 5 animals, and these 3 animals died from overdosing later. In the physical dependence direct induction test, animals received aniracetam (50 mg/kg) and sodium pentobarbital (25 mg/kg: the dose inducing intermediate CNS depression) intragastrically twice a day for 31 consecutive days. Abrupt withdrawal of aniracetam did not elicit abstinent signs (including changes in appetite and body weight) in all 6 animals, whereas withdrawal of pentobarbital produced typical abstinent behavioral signs and decreases in appetite and body weight. In conclusion, aniracetam was confirmed to develop neither physical dependence nor psychic dependence in cynomolgus monkeys.
PMID: 3570103, UI: 87192329
Piracetam, a new class of drug (nootropil) thought to enhance specific cognitive skills, was given in a 3300 mg daily dose to half of a group of fifty-five dyslexic boys aged 8-13 years, in a 12-week, double-blind, placebo-controlled study. The other half of the subjects received placebo. All subjects met the following criteria: normal intelligence, normal educational opportunities, no severe emotional problems, no neurological handicaps, good physical health, not taking other psychotropic medication, and scoring at least one and one half years below their mental age equivalent on the Gilmore Oral Reading Test. Non-verbal (auditory and visual) and verbal perceptual, and memory skills were examined, and reading, spelling, language and writing abilities were measured using standardized instruments. Compared to the placebo control group, individuals treated with Piracetam did not show statistically significant improvements above their baseline scores on measures of perception, memory, language, reading accuracy or comprehension, or writing accuracy. However, reading speed and numbers of words written in a timed period were significantly enhanced in subjects treated with Piracetam as compared to placebo. Effective reading and writing ability, taking both rate and accuracy into consideration, were also significantly improved in the Piracetam as compared to the placebo treatment group. The medication was well-tolerated and medical examinations showed no significant adverse reactions. These results encourage further study of Piracetam to determine more precisely the mechanism of action by which specific cognitive skills are affected.
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PMID: 3522509, UI: 86250260
Studies of 60 dyslexic boys age 8-14, carefully selected for exclusion of intellectual, sensory, psychiatric and neurological impairment and educational deprivation, were conducted to determine the efficacy of Piracetam, over a 12-week period, in improving reading and other related skills. There were no changes at the end of 12 weeks to distinguish the groups in accuracy or comprehension of prose-reading. Short-term memory gains, however, were recorded for the treated group on two different tests, digit span, and a test (Neimark) of immediate and delayed recall. The mean digit span scaled score for the entire group was one S.D. below their mean IQ. Considering only the performance of children whose digit span scaled scores were one S.D. or below the mean (7 or less), the treated group made a significant gain at the end of 12 weeks. On the Neimark test the treated group was significantly superior to the untreated group on first trial learning and they also lost significantly fewer object names after a delay. Improved retrieval from long-term storage could be demonstrated for the treated group on the rapid automatized naming test. Although there was no significant difference between the group at screening, the treated group was significantly faster on letter naming at the end of the drug trial. The treated group also improved their single word reading on the WRAT.
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PMID: 3522510, UI: 86250261
Following previous research which suggests that piracetam improves performance on tasks associated with the left hemisphere, a 12-week, double-blind, placebo-controlled study of developmental dyslexics was conducted. Six study sites treated 257 dyslexic boys between the ages of 8 and 13 years who were significantly below their potential in reading performance. Children were of at least normal intelligence, had normal findings on audiologic, ophthalmologic, neurologic, and physical examination, and were neither educationally deprived nor emotionally disturbed. Piracetam was found to be well tolerated in this study population. Children treated with piracetam showed improvements in reading speed. No other effects on reading were observed. In addition, improvement in auditory sequential short-term memory was observed in those piracetam-treated patients who showed relatively poor memory at baseline. It is suggested that longer term treatment with piracetam may result in additional improvements.
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PMID: 3900148, UI: 86009005
Piracetam possesses some properties not related to the nootropic activity. The purpose of the work was to study piracetam influence on effects of narcotic analgesics and opioid peptides at intracerebroventricular administration. In experiments on cats it was found that piracetam in a dose-dependent way prevented the emetic effect of morphine and leu-enkephalin. In experiments on rats (tail-flick test) piracetam was shown to be able of blocking the analgesic effect of fentanyl. Experiments on the study of the anticataleptogenic effect of piracetam also showed antagonism between piracetam and agonists of opioid receptors. Thus, it was shown on a number of models that piracetam exhibits antagonistic properties with respect of opioid peptides and narcotic analgesics.
PMID: 2897934, UI: 88242786
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, 466-8560, Nagoya, Japan.
[Medline
record in process]
Biochemical changes such as intracellular cAMP and Ca(2+) underlying morphine dependence and tolerance have been suggested. Therefore, we investigated the effects of nefiracetam (N-(2, 6-dimethyl-phenyl)-2(2-oxo-1-pyrrolidinyl) acetamide), which increases intracellular cAMP and Ca(2+) levels, on the development of morphine dependence and tolerance. Mice administered morphine (6 or 20 mg kg(-1)) twice daily for 5 days, showed withdrawal symptoms (jumping, diarrhea and body weight loss) after naloxone challenge (5 mg kg(-1)), indicating morphine dependence. Furthermore, tolerance to the analgesic effect of morphine was observed in these mice. Co-administration of nefiracetam (5 or 10 mg kg(-1)) with morphine during the pretreatment period, significantly reduced the signs of withdrawal symptoms, moreover, the tolerance was significantly attenuated. Elevation of cAMP levels in the cortex was observed in morphine-dependent mice, but not in mice co-administered nefiracetam. Acute administration of nefiracetam shows no effect on the withdrawal symptoms and the analgesic effect in morphine-naive mice. Theophylline (3 or 10 mg kg(-1)) tended to attenuate and enprofylline (10 or 30 mg kg(-1)) significantly attenuated the development of morphine dependence and tolerance. These findings suggest that co-administration of nefiracetam or compounds, which increase the cAMP level, may be a useful strategy for attenuating the development of morphine dependence and tolerance in the clinic.
PMID: 10996409, UI: 20452770
In the social interaction test of anxiety Piracetam (100 mg/kg) had an anxiolytic profile very similar to that seen after 5 days of administration of chlordiazepoxide (5 mg/kg). Piracetam (50-300 mg/kg) produced no signs of sedation and it was therefore suggested that it might be a non-sedative anxiolytic drug. Piracetam (100 mg/kg) produced significantly higher cortical concentrations of 5-hydroxytryptamine and lower concentrations of 5-hydroxyindoleacetic acid, indicating a reduced 5-HT turnover. There were no drug-induced changes in noradrenaline or dopamine in any brain region, either with or without pretreatment with alpha-methylparatyrosine. The cortical concentrations of 7 amino acids were measured and were unchanged by treatment with Piracetam.
PMID: 95599, UI: 82168483
In experiments on white male mice there was studied the influence of piracetam (250-300 mg/kg) on the analgesic effect of ligands of different types of opioid receptors (morphine, 7.5 mg/kg, DADLE, 7.5 mg/kg, pentazocine, 15 mg/kg) and also on the action of morphine concerning the cardiovascular system and respiration. Piracetam was shown to possess the antagonistic properties with respect to some effects of morphine, however they are not of the universal character and do not depend on the interaction with a certain type of opioid receptors.
PMID: 1973390, UI: 90316243
Ciba-Geigy Ltd., Pharmaceutical Research Department, Basle, Switzerland.
Oral pretreatment of mice with aldosterone or corticosterone blocked the memory-enhancing effects of piracetam, pramiracetam, aniracetam and oxiracetam in a dose-related manner, without, however, impairing the animals' learning performance. The improvement of memory induced by physostigmine, arecoline, and tacrine (THA) was similarly inhibited. The fact that elevated steroid levels suppress the memory-enhancing effects of entirely different substances could indicate that these substances have a common site of action. In the light of new observations showing increased cortisol concentrations in Alzheimer patients, this steroid dependency of the effects of memory enhancers might explain why only a limited number of these patients respond to therapy with nootropics or cholinomimetics.
PMID: 1410129, UI: 93029072
Institute of Physiology, Bulgarian Academy of Sciences.
The memory effects of citicholine (CCh) and piracetam (Pc) were tested in experiments on mice using the training method with passive avoidance and negative reinforcement (step-through). In single doses of 25, 50, 100 and 500 mg/kg, CCh applied one hour prior to training enhanced to the same degree and statistically significantly the retention of the memory traces in tests both 24 h and 7 days after the training session; Pc in a dose of 500 mg/kg improved the retention in memory tests 24 h after training, but had no significant effect during the tests 7 days after the training. Combined application of CCh and Pc in doses which are ineffective with respect to the memory process (CCh--10 mg/kg and Pc--200 mg/kg) caused a significant enhancement of the retention during the tests both 24 h and 7 days after the training. Scopolamine (2 mg/kg i.p.), applied 30 min prior to the training, manifested a marked amnestic effect during the tests 24 h after the training, but this effect was totally prevented if either CCh in a dose of 50 mg/kg or Pc in a dose of 500 mg/kg were applied before scopolamine. Citicholine in a dose of 100 mg/kg, as well as the combination of 50 mg/kg CCh and 500 mg/kg PC, not only completely prevented the scopolamine-induced amnesia, but they also significantly increased the retention of the memory traces in the scopolamine-treated mice compared with the retention observed in the control animals.
PMID: 2392950, UI: 90364913
Different groups of rats received combined or separate administration of different doses of piracetam (P1:100, P2:200, and P4:400 mg/kg) and choline (C1:100 and C2:200 mg/kg). Compared to control treatment, C1 significantly improved performance in a delayed alternation (DA) task, while P1, P2, P4 or P1C1 had no effect. Moreover, rats receiving P2C1 and P4C1 were significantly inferior in acquiring DA to rats receiving the vehicle or separate administration of P1, P2 or C1. The different treatments with combined or separate administration of P and C had no effect on spontaneous locomotor activity and two-way avoidance conditioning. In a recognition-task only groups C1 and P4 were able to discriminate between familiar and new objects. The combined or separate administration of P1 and C1 on NA, DA, DOPAC, 5-HT, 5-HIAA levels, CAT activity and choline uptake were measured in frontal cortex and hippocampus: the only significant effect was a 5-HT increase in the hippocampus of rats treated with C1.
PMID: 3110830, UI: 87261637
The effects of various piracetam + choline combinations on an experimental model of memory were investigated. Mice were given two sessions in a simple photo-cell activity cage and the decrease in activity at the second session (habituation) served as an index of retention. Retention was facilitated by post-session administration of 2000 mg/kg piracetam IP and 50 mg/kg piracetam + 50 mg/kg choline IP. Similar injections of choline alone (10 to 200 mg/kg IP), piracetam alone (10 to 1000 mg/kg IP) or other combinations of piracetam and choline were without effect. These results, consistent with those reported elsewhere, suggest that piracetam can interact with choline to facilitate memory processes in mice.
PMID: 6483933, UI: 85015088
In an attempt to gain some insight into possible approaches to reducing age-related memory disturbances, aged Fischer 344 rats were administered either vehicle, choline, piracetam or a combination of choline or piracetam. Animals in each group were tested behaviorally for retention of a one trial passive avoidance task, and biochemically to determine changes in choline and acetylcholine levels in hippocampus, cortex and striatum. Previous research has shown that rats of this strain suffer severe age-related deficits on this passive avoidance task and that memory disturbances are at least partially responsible. Those subjects given only choline (100 mg/kg) did not differ on the behavioral task from control animals administered vehicle. Rats given piracetam (100 mg/kg) performed slightly better than control rats (p less than 0.05), but rats given the piracetam/choline combination (100 mg/kg of each) exhibited retention scores several times better than those given piracetam alone. In a second study, it was shown that twice the dose of piracetam (200 mg/kg) or choline (200 mg/kg) alone, still did not enhance retention nearly as well as when piracetam and choline (100 mg/kg of each) were administered together. Further, repeated administration (1 week) of the piracetam/choline combination was superior to acute injections. Regional determinations of choline and acetylcholine revealed interesting differences between treatments and brain area. Although choline administration raised choline content about 50% in striatum and cortex, changes in acetylcholine levels were much more subtle (only 6-10%). No significant changes following choline administration were observed in the hippocampus. However, piracetam alone markedly increased choline content in hippocampus (88%) and tended to decrease acetylcholine levels (19%). No measurable changes in striatum or cortex were observed following piracetam administration. The combination of choline and piracetam did not potentiate the effects seen with either drug alone, and in certain cases the effects were much less pronounced under the drug combination. These data are discussed as they relate to possible effects of choline and piracetam on cholinergic transmission and other neuronal function, and how these effects may reduce specific memory disturbances in aged subjects. The results of these studies demonstrate that the effects of combining choline and piracetam are quite different than those obtained with either drug alone and support the notion that in order to achieve substantial efficacy in aged subjects it may be necessary to reduce multiple, interactive neurochemical dysfunctions in the brain, or affect activity in more than one parameter of a deficient metabolic pathway.
PMID: 7301036, UI: 82058347
Neurocybernetics Institute, Rostov State University, Rostov-on-Don, 344090, Russia. mam@krink.rnd.runnet.ru.
Adaptive effects of delta-sleep inducing peptide (DSIP, 12 microgram/100 g body weight, single intraperitoneal injection) and piracetam (3 mg/100 g body weight, daily intraperitoneal injection for 3 days) are manifested via differential changes in neurotransmitter amino acids (GABA, glutamate, aspartate), modulation of transport ATPase activity, and decreased accumulation of lipid peroxidation products (conjugated dienes, malonic dialdehyde, Schiff bases) in various fractions of neuronal membranes (myelin, synaptic and mitochondrial membranes) in the sensomotor cortex of rat brain. Under hyperbaric oxygenation (0.3 MPa for 2 h), the combination of DSIP and piracetam enhanced the protective effect of each compound.
PMID: 10395980, UI: 99327177
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
In experiments on rats using passive avoidance with punishment reinforcement (step-through) and two-way active avoidance with punishment reinforcement (shuttle-box), we examined the effects on acquisition and retention of different combinations of the nootropic drugs meclofenoxate (Mf), citicholine (CCh), piracetam (Pc), the structural analogues of aniracetam p-P and p-F, standardized extract from ginseng roots (PG) and the psychostimulants caffeine (Caf) and amphetamine (Amph). Favorable effects (more pronounced improvement of learning and/or memory as compared to that caused by the drugs when given alone) were in some cases obtained by the combination Mf+Caf, Pc+Caf, CCh+Caf, p-F+Caf, Mf+CCh, as well as by the combination Mf+PG applied to rats with electroconvulsive shock-induced amnesia. However, in some cases the combined administration of two drugs with favorable effects on memory did not led to summation or potentiation but rather to disappearance of these effects. This was observed under certain experimental conditions with some combinations of Caf and CCh, Mf, Pc and p-P and with some combinations of Amph and Mf. Based on our earlier results and data in the literature, we present some considerations about the role of the neurotransmitter mechanisms of action of the drugs tested as neurochemical correlates of their effects on memory. It is suggested that the unfavorable results obtained in some cases with combinations of nootropics and psychostimulants are due to the possible disturbance of selective acquisition by the psychostimulant drug.
PMID: 1688150, UI: 93034322