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Drugs & Aging

, Volume 1, Issue 1, pp 17–35 | Cite as

Piracetam

An Overview of its Pharmacological Properties and a Review of its Therapeutic Use in Senile Cognitive Disorders
  • Margaret W. Vernon
  • Eugene M. Sorkin
Drug Evaluation

Summary

Synopsis

Piracetam is the first of the socalled ‘nootropic’ drugs, a unique class of drugs which affect mental function. In animal models and in healthy volunteers, the drug improves the efficiency of the higher telencephalic functions of the brain involved in cognitive processes such as learning and memory.

The pharmacology of piracetam is unusual because it protects against various physical and chemical insults applied to the brain. It facilitates learning and memory in healthy animals and in animals whose brain function has been compromised, and it enhances interhemispheric transfer of information via callosal transmission. At the same time, even in relatively high dosages it is devoid of any sedative, analeptic or autonomic activities. How piracetam exerts its effects on memory disorders is still under investigation, although among other proposed mechanisms of action it is thought to facilitate central nervous system efficiency of cholinergic neurotransmission.

Results from trials involving elderly patients with senile cognitive disorders have been equivocal, as have the results obtained when piracetam has been combined with acetylcholine precursors. Piracetam seems to be almost completely devoid of adverse effects, and is extremely well tolerated.

In conclusion, opinion is divided as to the benefits of piracetam in the treatment of senile cognitive decline. Although double-blind studies in the elderly have produced mixed results, some such trials (particularly those involving larger numbers of patients) have reported favourable findings, thus offering some reason for cautious optimism in a notoriously difficult area of therapeutics. However, further investigations of piracetam alone and in combination therapy are required before any absolute conclusions can be drawn.

Pharmacological Properties

Piracetam is a cyclic derivative of γ-aminobutyric acid (GABA), and the first representative of what are commonly known as the ‘nootropic’ drugs. It has a protective effect on brain functions against externally applied brain ‘aggressions’, which include hypoxia, electroconvulsive treatment and barbiturate intoxication in experimental animals. It has been reported to facilitate learning and memory in several animal models as well as in aged animals. In electrophysiological and behavioural models, the drug facilitates cerebral inter- and intrahemispheric connectivity, indicating that it may enhance information transfer in the brain. Piracetam enhances microcirculation by reducing platelet activity, enhancing red blood cell deformability and reducing adherence of damaged erythrocytes to endothelial cells. In healthy volunteers, the drug enhances recall of learned information, increases verbal capacity and improves mental functioning under certain conditions. Piracetam stimulates glucose degradation in rat cortex slices, enhances 32P incorporation into brain phospholipids and stimulates adenylate cyclase. Although structurally related to GABA, it does not appear to have any similar GABA-like effects in animals. Its mechanism of action appears to be via stimulation of central cholinergic activity, although a number of other neurotransmitters may also be involved.

Pharmacokinetic Studies

Piracetam is completely absorbed after oral administration: peak plasma concentrations are reached after 30 to 40 minutes, and oral bioavailability is close to 100%. The elimination half-life of the drug in healthy volunteers is about 5 to 6 hours, but this may be increased in elderly patients, particularly those with multiple disease states. Piracetam is excreted unchanged in the urine, urinary excretion accounting for more than 98% of the administered dose. Distribution studies have shown that the drug is rapidly distributed in most essential organs. It crosses the blood-brain barrier, and is preferentially concentrated in the grey matter of the cerebrum and cerebellum, caudate nucleus, hippocampus, lateral geniculate body and chorioid plexus. Half-life in cerebrospinal fluid is greater than plasma half-life, indicating a tropism for brain tissue.

Therapeutic Trials

Double-blind controlled studies have produced mixed results with piracetam in the treatment of learning and memory disorders of the elderly. Comparison between different trials is difficult because of lack of standardisation of patient groups or assessment protocols. Although some improvements in memory and learning as a result of piracetam administration have been noted, these have been small and inconsistent. Because memory impairment in senile dementia is highly correlated with brain cholinergic function, trials have been carried out using piracetam and the acetylcholine precursors lecithin and choline. Although experiments in rats have shown that piracetam plus choline has a superior effect to either agent administered alone, results in human trials have been equivocal.

Adverse Effects

Piracetam is extremely well tolerated and generally free from adverse effects. Side effects which have been reported occasionally include mild dizziness, insomnia and nausea, but none of these have necessitated stopping therapy.

Dosage and Administration

Piracetam can be administered orally or intravenously in dosages ranging from 20 to 150 mg/ kg daily in divided doses. For long term treatment of senility, it is recommended that 2.4 to 4.8g orally be given daily, depending on the severity of the symptoms. In patients with impaired renal function, dosage regimens should be adjusted according to the manufacturer’s recommendations.

Keywords

Passive Avoidance Piracetam Aniracetam Oxiracetam Nootropic Drug 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • Margaret W. Vernon
    • 1
  • Eugene M. Sorkin
    • 1
  1. 1.Adis International Drug Information ServicesMairangi Bay, AucklandNew Zealand

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