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β-咔啉作为记忆研究工具:动物实验数据及推测

Beta-carbolines as tools in memory research: animal data and speculations.

作者信息

Sarter M, Stephens D N

机构信息

Research Laboratories, Department of Neuropsychopharmacology, Berlin, FRG.

出版信息

Psychopharmacol Ser. 1988;6:230-45. doi: 10.1007/978-3-642-73288-1_17.

Abstract

Benzodiazepines induce in animals, as in humans, almost exclusively anterograde amnesia. The mechanism of this effect is still unsettled; however, explanations like state dependency which may be based on sedative or emotional properties of benzodiazepines are usually favoured in contrast to an interpretation in terms of true amnesia. It is proposed that by the use of beta-carbolines with agonist, partial agonist, antagonist and partial inverse agonist properties, the nature of the amnesia induced by benzodiazepine receptor agonists may be characterised. From a series of experiments it is concluded that the major reason for benzodiazepine-induced amnesia might be an impaired ability to filter interfering stimuli; that is, an attentional deficit. Since the antagonist beta-carbolines may play a key role in providing evidence as to the GABAergic involvement in cognitive processes, the pharmacological profile of ZK 93426 is presented. The results of the interaction of beta-carbolines with scopolamine will provide a basis on which to speculate on the GABAergic control of cholinergic neurotransmission and its therapeutic implications.

摘要

苯二氮䓬类药物在动物身上,如同在人类身上一样,几乎只会引发顺行性遗忘。这种效应的机制尚未确定;然而,与基于真正遗忘的解释相比,诸如状态依存性等可能基于苯二氮䓬类药物镇静或情绪特性的解释通常更受青睐。有人提出,通过使用具有激动剂、部分激动剂、拮抗剂和部分反向激动剂特性的β-咔啉,可以对苯二氮䓬受体激动剂诱发的遗忘的性质进行表征。从一系列实验得出的结论是,苯二氮䓬类药物诱发遗忘的主要原因可能是过滤干扰性刺激的能力受损,即注意力缺陷。由于拮抗剂β-咔啉可能在提供关于γ-氨基丁酸能参与认知过程的证据方面发挥关键作用,因此介绍了ZK 93426的药理学特征。β-咔啉与东莨菪碱相互作用的结果将为推测γ-氨基丁酸能对胆碱能神经传递的控制及其治疗意义提供依据。

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