Arvat E, Giordano R, Grottoli S, Ghigo E
Department of Internal Medicine, University of Turin, Italy.
J Endocrinol Invest. 2002 Sep;25(8):735-47. doi: 10.1007/BF03345110.
Benzodiazepines (BDZ) are one of the most prescribed classes of drugs because of their marked anxiolytic, anticonvulsant, muscle relaxant and hypnotic effects. The pharmacological actions of BDZ depend on the activation of 2 specific receptors. The central BDZ receptor, present in several areas of the central nervous system (CNS), is a component of the GABA-A receptor, the activation of which increases GABAergic neurotransmission and is followed by remarkable neuroendocrine effects. The peripheral benzodiazepine receptors (PBR), structurally and functionally different from the GABA-A receptor, have been shown in peripheral tissues but also in the CNS, in both neurones and glial cells, and in the pituitary gland. BDZ receptors bind to a family of natural peptides called endozepines, firstly isolated from neurons and glial cells in the brain and then in several peripheral tissues as well. Endozepines modulate several central and peripheral biological activities, including some neuroendocrine functions and synthetic BDZ are likely to mimic them, at least partially. BZD, especially alprazolam (AL), possess a clear inhibitory influence on the activity of the HPA axis in both animals and humans. This effect seems to be mediated at the hypothalamic and/or suprahypothalamic level via suppression of CRH. The strong negative influence of AL on hypothalamicpituitary-adrenal (HPA) axis agrees with its peculiar efficacy in the treatment of panic disorders and depression. BZD have also been shown to increase GH secretion via mechanisms mediated at the hypothalamic or supra-hypothalamic level, though a pituitary action cannot be ruled out. Besides the impact on HPA and somatotrope function, BDZ also significantly affect the secretion of other pituitary hormones, such as gonadotropins and PRL, probably acting through GABAergic mediation in the hypothalamus and/or in the pituitary gland. In all, BDZ are likely to represent a useful tool to investigate GABAergic activity and clarify its role in the neuroendocrine control of anterior pituitary function; their usefulness probably overrides what had been supposed before.
苯二氮䓬类药物（BDZ）是处方量最大的药物类别之一，因其具有显著的抗焦虑、抗惊厥、肌肉松弛和催眠作用。BDZ的药理作用取决于两种特定受体的激活。中枢BDZ受体存在于中枢神经系统（CNS）的多个区域，是GABA - A受体的一个组成部分，其激活会增加GABA能神经传递，并随之产生显著的神经内分泌效应。外周苯二氮䓬受体（PBR）在结构和功能上与GABA - A受体不同，已在外周组织以及CNS的神经元、胶质细胞和垂体中被发现。BDZ受体与一类名为内源性苯二氮䓬的天然肽结合，这类肽最初是从大脑中的神经元和胶质细胞中分离出来的，随后也在多个外周组织中被发现。内源性苯二氮䓬调节多种中枢和外周生物活性，包括一些神经内分泌功能，合成的BDZ可能至少部分地模拟它们的作用。BZD，尤其是阿普唑仑（AL），对动物和人类的下丘脑 - 垂体 - 肾上腺（HPA）轴的活性具有明显的抑制作用。这种作用似乎是通过抑制促肾上腺皮质激素释放激素（CRH）在下丘脑和/或下丘脑以上水平介导的。AL对下丘脑 - 垂体 - 肾上腺（HPA）轴的强烈负面影响与其在治疗惊恐障碍和抑郁症方面的特殊疗效一致。BZD还被证明可通过下丘脑或下丘脑以上水平介导的机制增加生长激素（GH）的分泌，不过垂体的作用也不能排除。除了对HPA和生长激素功能的影响外，BDZ还显著影响其他垂体激素的分泌，如促性腺激素和催乳素，可能是通过下丘脑和/或垂体中的GABA能介导作用。总之，BDZ可能是研究GABA能活性并阐明其在前垂体功能神经内分泌控制中作用的有用工具；它们的有用性可能超过了之前的预期。
