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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.
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.
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.
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.
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.
KeywordsPassive Avoidance Piracetam Aniracetam Oxiracetam Nootropic Drug
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- Aantaa E, Meurman OH. The effect of piracetam (nootropil, UCB-6215) upon the late symptoms of patients with head injuries. Journal of International Medical Research 3: 352–355, 1975Google Scholar
- Abuzzahab Sr FS, Merwin GE, Zimmermann RL, Sherman MC. A double-blind investigation of piracetam (nootropil) versus placebo in the memory of geriatric inpatients. Psychopharmacology Bulletin 14: 23–26, 1978Google Scholar
- Armstrong A. Recent trends in research on Alzheimer’s disease. Scrip, 1986Google Scholar
- Bering B, Müller WE. Interaction of piracetam with several neurotransmitter receptors in the central nervous system. Relative specificity for 3H-glutamate sites. Arzneimittel-Forschung 35(2): 1350–1352, 1985Google Scholar
- Bick RL, Fareed J, Skondia V. Piracetam: a new platelet suppressing drug. Abstract. Thrombosis and Haemostasis 46: 67, 1981Google Scholar
- Bryant RC, Petty F, Byrne WL. Effects of piracetam (SKF 38462) on acquisition, retention and activity in the goldfish. Pharmacologia 29(2): 121–130, 1973Google Scholar
- Cavazzuti L, Bertoldin T, Volpe D, Crepaldi G. Influence of treatment with piracetam on psychocognitive decline in elderly hospitalized patients. In Symposium on Piracetam: 5 years’ progress in pharmacology and clinics, pp. 67–74, Technicas Graficas Forma, Madrid, 1990Google Scholar
- Comely M, Henkel E, Künzel W, Zimmermann P. Pharmacokinetic of piracetam during labour influence to acid-base-status in material and fetal blood. Zeitschrift für Geburtshilfe und Perinatologie 181: 199–205, 1977Google Scholar
- Dimond SJ. Use of a nootropic substance to increase the capacity for verbal learning and memory in normal man. 3rd Congress of the International College of Psychosomatic Medicine, 1975Google Scholar
- Fcrnandes CMC, Samuel J. The use of piracetam in vertigo. South African Medical Journal 11: 806–808, 1985Google Scholar
- Gedye JL, Ibrahimi GS, McDonald C. Double blind controlled trial of piracetam (2-pyrrolidone acetamide) on two groups of psychogeriatric patients. IRCS Medical Science: Clinical Medicine; Clinical Pharmacology and Therapeutics; Psychology and Psychiatry; Social and Occupational Medicine 2: 202, 1978Google Scholar
- Giurgea C, Lefevre D, Lescrenier C, David-Remacle M. Pharmacological protection against hypoxia-induced amnesia in rats. Psychopharmacologia (Berl) 20: 160–168, 1971Google Scholar
- Giurgea C, Moyersoons F. Differential pharmacological reactivity of three types of cortical evoked potentials. Archives Internationals de Pharmacodynamie et de Thérapie 188: 401–404, 1970Google Scholar
- Giurgea C, Moyersoons F. Contribution to the experimental pharmacotherapy of acute drug intoxications. Journal of Pharmacology 5 (Suppl. 2): 37, 1974Google Scholar
- Giurgea C, Salama M. Nootropic drugs. Progress in Neuro-Psychopharmacology and Biological Psychiatry 1: 235–247, 1977Google Scholar
- Gobert JG. Gènese d’un medicament: le piracetam métabolisation et recherche biochimique. Journal de Pharmacie de Belgique 27: 281–304, 1972Google Scholar
- Gobert JG, Baltes EL. Availability and plasma clearance of piracetam in man. Farmaco 2: 83–91, 1977Google Scholar
- Hassmannová J, Mysliveček J, Romoliniovà A. Learning and memory in the ontogeny of rats given piracetam. Activitas Nervosa Superior 22: 95–96, 1980Google Scholar
- Henry RL, Nalbandian RM, Dzandu JK. Effect of membrane-bound protein phosphorylation of intact normal and diabetic human erythrocytes: enhanced membrane deformability. Diabetes 30 (Suppl. 1): 83a, 1981Google Scholar
- Hronek J. Drahokoupil L, Fait V, Hudeovà T, Laciga Z, et al. Clinical experience with piracetam therapy in gerontology. Comm. 21st Annual Psychopharmacology Meeting, Tchécoslovaquie, Jesenir, pp. 121–129, 1979Google Scholar
- Israel L. Memory training programs (MTPs) combined with drug therapy in primary care, including patients with age-associated memory impairment. In Symposium on Piracetam: 5 years’ progress in pharmacology and clinics, pp. 17–22, Technicas Graficas Forma, Madrid, 1990Google Scholar
- Koupilová M, Fusek J, Hrdina V, Herink J. Piracetam effect on learning and memory in rats. Activitas Nervosa Superior 22: 193–194, 1980Google Scholar
- Kruse H, Konler H. Memory enhancing effects of piracetam in aged rats. Abstract. Federation Proceedings 37: 888, 1978Google Scholar
- Lenègre A, Chermat R, Avril I, Stéru L, Porsolt RD. Specificity of piracetam’s anti-amnesic activity in three models of amnesia in the mouse. Pharmacology, Biochemistry and Behavior 29: 625–629, 1988Google Scholar
- Macchione C, Molaschi M, Fabris F, Feruglio FS. Results with piracetam in the management of senile psycho-organic syndromes. Acta Therapeutica 2: 261–269, 1976Google Scholar
- Mares P, Marešová D. Effect of piracetam on excitability cycle of cortical interhemispheric responses in the rat. Activitas Nervosa Superior (Praha) 27(4): 285–286, 1985Google Scholar
- Marešová D, Mareš P. Effect of piracetam on cortical epileptogenic foci in the rat. Activitas Nervosa Superior 26: 67–68, 1984Google Scholar
- Marin Perez GM. Evaluation of the clinical effects of piracetam in the deterioration of the intellectual functions of a geriatric population: a double-blind study. 2nd International Symposium on Nootropic Drugs, Mexico, May 21–22, 1981Google Scholar
- Moos WH, Hershenson FM. Potential therapeutic strategies for senile cognitive disorders. Drug News and Perspectives 2: 397–409, 1989Google Scholar
- Müller WE, Pilch H, Stoll L, Schubert T. Piracetam as a possible cell communication modulator — focus on central M-cholinoceptors. Pharmazeutische Zeitung 3: 1–8, 1990Google Scholar
- Mysliveček J, Hassmannová J. Effect of piracetam on learning and brain potentials in rats with early sensory deprivation. Risks of Psychotropic Drugs 19: 171–175, 1975Google Scholar
- Nikolova M, Nikolov R, Tsikalova R, Popivanov D. Piracetam effect on the visual evoked potentials in cats. Drugs Under Experimental and Clinical Research 6(7): 33–37, 1980Google Scholar
- Olpe H-R, Pozza MF, Jones RSG, Haas HL. Comparative electrophysiological investigations on oxiracetam and piracetam. Clinical Neuropharmacology 9 (Suppl. 3): 48–55, 1986Google Scholar
- Parrisius HW. Doppelblindstudie mit Piracetam in der Geriatrie. Geriatrie 7(1): 32–37, 1977Google Scholar
- Passeri M. A multicentre study of piracetam in patients with late-onset senile dementia. In Symposium on Piracetam: 5 years’ progress in pharmacology and clinics, pp. 75–80, Technicas Graficas Formas, Madrid, 1990Google Scholar
- Pede JP, Schimpfessel L, Grokaert R. The action of piracetam on the oxidative phosphorylation. Archives Internationales de Physiologie et de Biochimie 79: 1036–1037, 1971Google Scholar
- Piercey MF, Vogelsang GD, Franklin SR, Tang AH. Reversal of scopolamine-induced amnesia and alterations in energy metabolism by the nootropic piracetam: implications regarding identification of brain structures involved in consolidation of memory traces. Brain Research 424: 1–9, 1987PubMedGoogle Scholar
- Pomara N, Block R, Moore N, Rhiew HB, Berchou R, et al. Combined piracetam and cholinergic precursor treatment for primary degenerative dementia. IRCS Medical Science 12: 388–389, 1984Google Scholar
- Pomara N, Reisberg B, Ferris SH, Gershan S. Drug treatment in cognitive decline. In Maletta GJ, Pirozzolo FJ(Eds) Advances in neurogerontology, Praeger, New York, 1981Google Scholar
- Reisberg B, Ferris SH, Schneck MK, Corwin J, Mir P, et al. Piracetam in the treatment of cognitive impairment in the elderly. Drug Development Research 2: 475–480, 1982Google Scholar
- Reuse-Blom S, Polderman J. Influence of piracetam upon the pial micro-circulation. In Loose & Loose(Eds) 6th International Angiography and Angiology Seminar, Baden-Baden, March 15–17, 1979. Verlag-Gerhard Witzstrock, Köln, 1980Google Scholar
- Schmidt U, Brendemühl D, Engels K, Sehenk N, Ludemann E. Piracetam and the driving behaviour of elderly motorists in standardized test runs under road traffic conditions. Symposium on Piracetam: 5 years’ progress in pharmacology and clinics, pp. 47–60, Technicas Graficas Formas, Madrid, 1990Google Scholar
- Schulz H-U, Wittler Th. Age-related changes in pharmacokinetics of 2-oxo-pyrrolidine-l-acetamide (piracetam) in man. Abstract 211. Naunyn-Schmiedeberg’s Archives of Pharmacology 313 (Suppl.): R53, 1980Google Scholar
- Serby M, Corwin J, Rotrosen J, Ferris SH, Reisberg B, et al. Lecithin and piracetam in Alzheimer’s disease. Psychopharmacology Bulletin 19: 126–129, 1983Google Scholar
- von Dorn M. Piracetam bei vorzeitiger biologischer Alterung: doppelblind-prüfung nach medikamentöser Vorselektion. Fortschritte der Medizin 96: 1525–1530, 1978Google Scholar
- von Kretschmar JH, Kretschmar L. On the dose-effect relationship in the therapy with piracetam. Arzneimittel-Forschung 26: 1158–1159, 1976Google Scholar
- von Ostrowski J, Keil M. Autoradiographische Untersuchungen zur Verteilung von 14C-Piracetam im Affengehirn. Arzneimittel-Forschung 28(1): 29–35, 1978Google Scholar
- von Ostrowski J, Keil M, Schraven E. Autoradiographische Untersuchungen zur Verteilung von Piracetam-14C bei Ratte und Hund. Arzneimittel-Forschung 25: 589–596, 1975Google Scholar
- von Woelk H. Zum Einfluss von Piracetam auf die neuronale und synaptosomale Phospholipase-A2-Aktivität. Arzneimittel-Forschung 29(1): 615–618, 1979Google Scholar
- Voronina TA, Krapivin SV, Nerobkova LN. Specificity of action of pyracetam, pyritinol, and cleregil on the transcallosal evoked potential. Bulletin of Experimental Biology and Medicine 101: 326–329, 1986Google Scholar
- Wahl M, Kuschinsky W. Report on the study of the direct vaso-active action of piracetam upon the cerebral vascular system of the cat. In Loose & Loose (Eds) 6th International Angiography and Angiology Seminar, Baden-Baden, March 15–17, 1979. Verlag Gerhard Witzstrock, Köln, 1980Google Scholar
- Wolthuis OL, Nickolson VJ. Piracetam and acquisition behaviour in rats: electrophysiological and biochemical effects. 3rd Congress International College of Psychosomatic Medicine, Rome: 135–149, 1975Google Scholar
- Yamada K, Inoue T, Tanaka M, Furukawa T. Prolongation of latencies for passive avoidance responses in rats treated with aniracetam or piracetam. Pharmacology, Biochemistry and Behavior 22: 645–648, 1985Google Scholar