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[苯二氮䓬类药物的分子生物学作用机制]

[The molecular biology mechanism of action of benzodiazepine].

作者信息

Krug G

机构信息

Klinik für Anästhesiologie und Intensivtherapie, Medizinische Fakultät (Charité), Humboldt-Universität zu Berlin.

出版信息

Anaesthesiol Reanim. 1993;18(1):24-30.

PMID:8395853
Abstract

The central GABAA synapses contain specific benzodiazepine binding sites thought to modulate the receptor allosterically for the transmitter. The benzodiazepine receptor represents a modulating site which is located on the GABA-A receptor/chloride channel complex and mediates both positive and negative modulation of the chloride channel. The effects of the benzodiazepines lie in an increase in the receptor-coupled conductivity of chlorides. Different stressors induce changes in the benzodiazepine receptor complex regarding hypersensitivity. There are indications that these stress-induced changes are mediated by an endogenous peptide. The modulation on these receptors is of functional significance in stress-relevant behavioural reactions and in conflict situations. The research results have led to new concepts of the receptor function and of the effects of compounds which are the basis of potential pharmaceuticals. The neuro-pharmacology of the future promises new pharmaceutical targets on the mechanisms of the allosteric modulation of the receptor function.

摘要

中枢GABAA突触含有特定的苯二氮䓬结合位点,据认为这些位点可通过变构调节来调控递质的受体。苯二氮䓬受体代表一个位于GABA-A受体/氯离子通道复合物上的调节位点,介导氯离子通道的正性和负性调节。苯二氮䓬类药物的作用在于增加受体偶联的氯离子传导性。不同的应激源会导致苯二氮䓬受体复合物出现超敏反应的变化。有迹象表明,这些应激诱导的变化是由一种内源性肽介导的。这些受体上的调节在与应激相关的行为反应和冲突情境中具有功能意义。这些研究结果催生了关于受体功能以及作为潜在药物基础的化合物作用的新概念。未来的神经药理学有望在受体功能变构调节机制方面找到新的药物靶点。

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