PIRACETAM AND OTHER STRUCTURALLY RELATED NOOTROPICS

Nearly three decades have now passed since the discovery of the pirace tam-like nootropics, compounds which exhibit cognition-enhancing prope rties, but for which no commonly accepted mechanism of action has been established. This review covers clinical, pharmacokinetic, biochemica l and behavioural results presented in the literature from 1965 throug h 1992 (407 references) of piracetam, oxiracetam, pramiracetam, etirac etam, nefiracetam, aniracetam and rolziracetam and their structural an alogues. The piracetam-like nootropics are capable of achieving revers al of amnesia induced by, e.g., scopolamine, electroconvulsive shock a nd hypolda. Protection against barbiturate intoxication is observed an d some benefit in clinical studies with patients suffering from mild t o moderate degrees of dementia has been demonstrated. No affinity for the alpha(1)-, alpha(2)-, beta-, muscarinic, 5-hydroxytryptamine-, dop amine, adenosine-A(1)-, mu-opiate, gamma-aminobutyric acid (GABA) (exc ept for nefiracetam (GABA(A))), benzodiazepine and glutamate receptors has been found. The racetams possess a very low toxicity and lack ser ious side effects. Increased turnover of different neurotransmitters h as been observed as well as other biochemical findings, e.g., inhibiti on of enzymes such as prolylendopeptidase. So far, no generally accept ed,mechanism of action has, however, emerged. We believe that the effe ct of the racetams is due to a potentiation of already present neurotr ansmission and that much evidence points in the direction of a modulat ed ion flux by, e.g., potentiated calcium influx through non-L-type vo ltage-dependent calcium channels, potentiated sodium influx through lp ha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor gated c hannels or voltage-dependent channels or decreases in potassium efflux . Effects on carrier mediated ion transport are also possible.