Taylor D P, Moon S L
CNS Biology, Bristol-Myers Squibb Company, Wallingford, CT 06492-7660.
Neuropeptides. 1991 Jul;19 Suppl:15-9. doi: 10.1016/0143-4179(91)90078-w.
The desire of the pharmaceutical industry to obtain more selective agents for the treatment of anxiety with fewer or diminished side effects and a profile consistent with safety during long-term use resulted in a search which has identified the azapirones as a new class of anxiolytics which lack structural or biochemical homology with the benzodiazepines. This presentation reviews the efficacy of buspirone (BuSpar), the first of this class to reach wide acceptance, and its analogs, gepirone, ipsapirone, and tandospirone, in the clinical treatment of anxiety and compares their 'anxioselective' profiles to those of the benzodiazepines. The azapirones appear to act as serotonin 5-HT1A partial agonists as they all share high affinity for 5-HT1A binding sites in vitro as well as in anatomical studies. Moreover, their biochemical, electro-physiological, and behavioural actions are consistent with this suggestion. That the serotonergic actions of the azapirones are relevant to their anxiolytic efficacy is suggested by their efficacy in animal models sensitive to other effective anxiolytics as well as their loss of efficacy in such testing following lesions of serotonergic neurons. Thus action upon serotonergic neurotransmission may produce a highly desirable anxioselective profile of effects.
制药行业渴望获得更具选择性的药物来治疗焦虑症，这类药物副作用更少或副作用减轻，且长期使用时安全性良好，这促使人们展开了一系列研究，最终确定了氮杂螺环癸烷二酮类药物是一类新型抗焦虑药，它们与苯二氮䓬类药物在结构或生化方面没有同源性。本报告回顾了丁螺环酮（布斯帕）（该类药物中首个获得广泛认可的药物）及其类似物吉哌隆、伊沙匹隆和坦度螺酮在焦虑症临床治疗中的疗效，并将它们的“抗焦虑选择性”特征与苯二氮䓬类药物进行了比较。氮杂螺环癸烷二酮类药物似乎作为5-羟色胺5-HT1A部分激动剂发挥作用，因为它们在体外以及解剖学研究中对5-HT1A结合位点都具有高亲和力。此外，它们的生化、电生理和行为学作用都与这一推测相符。氮杂螺环癸烷二酮类药物的5-羟色胺能作用与其抗焦虑疗效相关，这一观点得到了以下证据的支持：它们在对其他有效抗焦虑药敏感的动物模型中具有疗效，以及在5-羟色胺能神经元受损后的此类测试中失去疗效。因此，作用于5-羟色胺能神经传递可能会产生一种非常理想的抗焦虑选择性效应特征。
