Simmonds M A
Nature. 1980 Apr 10;284(5756):558-60. doi: 10.1038/284558a0.
The benzodiazepines have been well characterised as minor tranquillizers and attempts to explain their unique spectrum of activity have included suggestions that they may interact with a variety of neurotransmitter systems. Recently, a possible interaction with the gamma-aminobutyric acid (GABA) system has received most attention. Benzodiazepines potentiate the actions of both synaptically released and exogenously administered GABA on mammalian neuronal preparations but the site of action within the GABA response mechanism has not been determined. Binding studies suggest that benzodiazepines combine with highly specific sites in the neuronal membrane and that these sites have some indirect association with GABA receptors. To investigate this association further in a functioning GABA system, quantitative studies have been made in vitro on neuronal depolarisations mediated by GABA receptor activation. Evidence has already been presented that bicuculline is most probably a competitive antagonist at the GABA receptor while picrotoxin acts as an antagonist at a separate site. Here flurazepam is shown to attenuate preferentially the action of picrotoxin rather than bicuculline and a model is suggested for the site of action of these drugs within the GABA response mechanism.
苯二氮䓬类药物已被明确归类为弱安定药，关于解释其独特活性谱的尝试包括：有人提出它们可能与多种神经递质系统相互作用。最近，与γ-氨基丁酸（GABA）系统的可能相互作用受到了最多关注。苯二氮䓬类药物可增强突触释放的以及外源性给予的GABA对哺乳动物神经元制剂的作用，但在GABA反应机制中的作用位点尚未确定。结合研究表明，苯二氮䓬类药物与神经元膜中的高度特异性位点结合，且这些位点与GABA受体存在某种间接关联。为了在功能性GABA系统中进一步研究这种关联，已在体外对由GABA受体激活介导的神经元去极化进行了定量研究。已有证据表明，荷包牡丹碱很可能是GABA受体的竞争性拮抗剂，而印防己毒素则在另一个位点起拮抗剂作用。在此表明，氟西泮优先减弱印防己毒素的作用而非荷包牡丹碱的作用，并提出了这些药物在GABA反应机制中的作用位点模型。
