RECEPTORS IN THE CENTRAL NERVOUS SYSTEM--BIOCHEMISTRY TO BEHAVIOR

苯二氮卓类药物的高亲和力和立体特异性受体 在哺乳动物的中枢神经系统中。目前认为， 苯二氮卓类药物与其受体的相互作用引发一系列 导致GABA介导的氯化作用增强的神经元事件 渗透性。后者在行为上导致了主要的药理作用 苯二氮类药物的作用，即它们的抗焦虑、抗惊厥、 催眠和肌肉松弛作用。除了苯二氮类药物外，还有一种 多种次要镇静剂类别的镇静/催眠剂(例如， 巴比妥酸盐)似乎与 苯二氮卓类/GABA受体复合体，因此提出了后者 作为轻微镇静剂作用的常见部位。的几个方面 目前正在研究苯二氮卓类/GABA受体复合体，包括 受体的纯化、多个结合位点的鉴定 识别激动剂、拮抗剂或相反药物的受体复合体 激动剂。针对多种肿瘤的抗碘独特型抗体的研究进展 结合部位结构域对复合体的行为和功能的研究 新型(非苯二氮卓类)抗焦虑药物的生化效应 “焦虑性”反向激动剂，以及一种新的 中枢和外周组织中苯二氮卓类受体的表达 4-氯安定(Ro5-4864)，即所谓的外周苯二氮卓 受体配体。最近的工作也集中在使用体外系统 用于测量亚细胞制剂中GABA受体-效应器的偶联 来自大鼠脑(突触神经体)。这项技术有很大的优势 巴比妥酸盐和GABA受体介导的氯离子通量的易化研究 并形成了第一个可靠的方法来研究其功能 体外的GABA受体。

High affinity and stereospecific receptors for benzodiazepines are present in the mammalian central nervous system. It is currently believed that the interaction of benzodiazepines with their receptors initiates a series of neuronal events resulting in an enhancement of GABA-mediated choloride permeability. The latter results behaviorally in the major pharmacological actions of benzodiazepines, namely their anxiolytic, anticonvulsant, hypnotic, and muscle relaxant actions. In addition to benzodiazepines, a variety of sedative/hypnotic agents of the minor tranquilizer class (e.g., the barbiturates) appear to interact with one or more components of the benzodiazepine/GABA receptor complex, and thus the latter has been proposed as a common site of minor tranquilizer action. Several aspects of the benzodiazepine/GABA receptor complex are currently being studied, including purification of the receptor, characterization of multiple binding sites on the receptor complex which recognizes agonist, antagonists or inverse agonists. The development of anti-iodiotypic antibodies to the various binding site domains on the complex studies on the behavioral and biochemical effects of novel (non-benzodiazepine) anxiolytics as well as "anxiogenic" inverse agonists, and the identification of a novel benzodiazepine receptor in the CNS and peripheral tissues for 4-chlorodiazepam (Ro5-4864), the so-called peripheral benzodiazepine receptor ligand. Recent work has also focused on using an in vitro system for measuring GABA receptor-effector coupling in a subcellular preparation from rat brain (the synaptoneurosome). This technique has greatly facilitated studies on barbiturate and GABA receptor-mediated chloride flux and has resulted in the first reliable method for studying the function of the GABA receptor in vitro.