PIRACETAM AND OTHER STRUCTURALLY RELATED NOOTROPICS

被引:256
作者
GOULIAEV, AH
SENNING, A
机构
[1] ENGN ACAD DENMARK, DEPT CHEM & CHEM ENGN, DK-2800 LYNGBY, DENMARK
[2] AARHUS UNIV, DEPT CHEM, DK-8000 AARHUS C, DENMARK
关键词
MEMORY; COGNITION; NOOTROPICS; PIRACETAM DERIVATIVE; MECHANISM; MEMBRANE EXCITABILITY; PHARMACOKINETICS;
D O I
10.1016/0165-0173(94)90011-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Nearly three decades have now passed since the discovery of the piracetam-like nootropics, compounds which exhibit cognition-enhancing properties, but for which no commonly accepted mechanism of action has been established. This review covers clinical, pharmacokinetic, biochemical and behavioural results presented in the literature from 1965 through 1992 (407 references) of piracetam, oxiracetam, pramiracetam, etiracetam, nefiracetam, aniracetam and rolziracetam and their structural analogues. The piracetam-like nootropics are capable of achieving reversal of amnesia induced by, e.g., scopolamine, electroconvulsive shock and hypolda. Protection against barbiturate intoxication is observed and some benefit in clinical studies with patients suffering from mild to moderate degrees of dementia has been demonstrated. No affinity for the alpha(1)-, alpha(2)-, beta-, muscarinic, 5-hydroxytryptamine-, dopamine, adenosine-A(1)-, mu-opiate, gamma-aminobutyric acid (GABA) (except for nefiracetam (GABA(A))), benzodiazepine and glutamate receptors has been found. The racetams possess a very low toxicity and lack serious side effects. Increased turnover of different neurotransmitters has been observed as well as other biochemical findings, e.g., inhibition of enzymes such as prolylendopeptidase. So far, no generally accepted,mechanism of action has, however, emerged. We believe that the effect of the racetams is due to a potentiation of already present neurotransmission and that much evidence points in the direction of a modulated ion flux by, e.g., potentiated calcium influx through non-L-type voltage-dependent calcium channels, potentiated sodium influx through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor gated channels or voltage-dependent channels or decreases in potassium efflux. Effects on carrier mediated ion transport are also possible.
引用
收藏
页码:180 / 222
页数:43
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