De Souza E B
Laboratory of Neurobiology, Neuroscience Branch, NIDA Addiction Research Center, Baltimore, MD 21224.
J Psychiatr Res. 1990;24 Suppl 2:111-9. doi: 10.1016/0022-3956(90)90042-o.
Benzodiazepine administration has been associated with alterations in neuroendocrine function both in experimental animals and in humans. Clinical and laboratory data indicate that the beta-carbolines, a class of active benzodiazepine receptor inverse agonists, cause behavioral and neuroendocrine changes characteristic of anxiety and stress. In contrast, the "classic" benzodiazepine receptor agonists such as diazepam can reduce anxiety and inhibit stress-induced increases in anterior pituitary hormone secretion. Although the site of action and mechanisms by which benzodiazepines alter anterior pituitary hormone secretion are still under investigation, evidence suggests that the effects are mediated in the brain, primarily through actions at benzodiazepine receptors in the hypothalamus. The benzodiazepines may act at GABA-coupled benzodiazepine receptors in the hypothalamus or other regions of the brain to potentiate the effects of endogenous GABA. It also is believed that brain monoamines may modulate the effects of endogenous GABA. Brain monoamines have also been reported to modulate the effects of benzodiazepines on stress-induced hypothalamic-pituitary-adrenocortical function. Direct effects of the benzodiazepines on central- and peripheral-type benzodiazepine receptors in the anterior pituitary have also been documented.
在实验动物和人类中，苯二氮䓬类药物的使用都与神经内分泌功能的改变有关。临床和实验室数据表明，β-咔啉类物质，一类活性苯二氮䓬受体反向激动剂，会引起焦虑和应激特有的行为及神经内分泌变化。相比之下，“经典”的苯二氮䓬受体激动剂，如地西泮，可减轻焦虑并抑制应激诱导的垂体前叶激素分泌增加。尽管苯二氮䓬类药物改变垂体前叶激素分泌的作用位点和机制仍在研究中，但有证据表明其作用是在大脑中介导的，主要通过作用于下丘脑的苯二氮䓬受体。苯二氮䓬类药物可能作用于下丘脑或大脑其他区域的γ-氨基丁酸（GABA）偶联苯二氮䓬受体，以增强内源性GABA的作用。人们还认为脑单胺可能调节内源性GABA的作用。据报道，脑单胺也可调节苯二氮䓬类药物对应激诱导的下丘脑-垂体-肾上腺皮质功能的影响。苯二氮䓬类药物对垂体前叶中枢型和外周型苯二氮䓬受体的直接作用也已得到证实。
