Mendelson W B
Psychiatr Dev. 1984 Autumn;2(3):161-77.
The discovery of high affinity, stereoselective binding sites for benzodiazepines (BZ) was a major step in understanding the molecular mechanism by which these widely used sedative/hypnotics exert their various pharmacologic effects. It has become clear that the BZ receptor complex has functional significance in terms of the anxiolytic, anticonvulsant and muscle relaxant properties of these widely used compounds. Until recently its role in the sleep-inducing properties has been unclear. This paper reviews a series of studies indicating that the BZ receptor complex does indeed mediate the hypnotic effects of flurazepam, and that these effects may involve alterations in calcium flow across neuronal membranes. Preliminary evidence also suggests that some pharmacologic properties of barbiturates may involve interactions with portions of the benzodiazepine receptor complex. Lethality from pentobarbital in mice, for instance, can be greatly reduced by treatment with IPPO, a compound which binds in relation to the chloride ionophore. The implications of sub-types of BZ receptors are discussed. Experience with some compounds which bind at the BZ receptor suggests that in the future drugs may become available which are much more specific for individual desired effects.
苯二氮䓬（BZ）高亲和力、立体选择性结合位点的发现是理解这些广泛使用的镇静/催眠药发挥其各种药理作用的分子机制的重要一步。现已明确，就这些广泛使用的化合物的抗焦虑、抗惊厥和肌肉松弛特性而言，BZ受体复合物具有功能意义。直到最近，其在诱导睡眠特性中的作用仍不明确。本文综述了一系列研究，这些研究表明BZ受体复合物确实介导了氟西泮的催眠作用，并且这些作用可能涉及跨神经元膜的钙流改变。初步证据还表明，巴比妥类药物的一些药理特性可能涉及与苯二氮䓬受体复合物部分的相互作用。例如，用IPPO（一种与氯离子载体结合的化合物）治疗可大大降低戊巴比妥对小鼠的致死率。文中还讨论了BZ受体亚型的意义。一些与BZ受体结合的化合物的经验表明，未来可能会有对个体所需效果更具特异性的药物。
