Taylor D P
CNS Biology, Pharmaceutical Research and Development Division, Bristol-Myers Company, Wallingford, Connecticut 06492.
FASEB J. 1988 Jun;2(9):2445-52. doi: 10.1096/fasebj.2.9.2836252.
Anxiety has historically been treated by agents with a sedative component to their action. In the last decade or so it has been determined that gamma-aminobutyric acid (GABA) receptors may mediate the anxiolytic actions of the benzodiazepines, propanediol carbamates, barbiturates, and ethanol. However, inasmuch as these drugs have additional pharmacological properties (sedation, muscle relaxation, seizure control), the search for an anxioselective drug was continued. Buspirone appears to be such a drug. Clinical studies have clearly demonstrated the efficacy of buspirone in the treatment of generalized anxiety disorder without the ancillary pharmacology of earlier anxiolytics. Buspirone does not act on the GABA receptor. Rather, its most salient interaction with neurotransmitter receptors occurs at the 5-HT1A serotonin receptor. This action is supported by studies focused on receptor binding, anatomical localization, biochemistry, neurophysiology, and animal behavior. The recognition that action at 5-HT1A receptors may be a viable approach to the pharmacotherapy of anxiety is evidenced by the number of other agents of this class under development by a number of pharmaceutical companies.
从历史上看，焦虑症一直通过具有镇静作用的药物进行治疗。在过去十年左右的时间里，人们已经确定γ-氨基丁酸（GABA）受体可能介导苯二氮䓬类、丙二醇氨基甲酸酯类、巴比妥类药物以及乙醇的抗焦虑作用。然而，由于这些药物具有其他药理特性（镇静、肌肉松弛、癫痫控制），因此人们继续寻找一种抗焦虑选择性药物。丁螺环酮似乎就是这样一种药物。临床研究清楚地证明了丁螺环酮在治疗广泛性焦虑症方面的疗效，且没有早期抗焦虑药物的辅助药理学作用。丁螺环酮不作用于GABA受体。相反，它与神经递质受体最显著的相互作用发生在5-HT1A血清素受体上。专注于受体结合、解剖定位、生物化学、神经生理学和动物行为的研究支持了这一作用。许多制药公司正在研发的这类其他药物的数量证明，作用于5-HT1A受体可能是焦虑症药物治疗的一种可行方法。
