Montgomery S A
J Clin Psychiatry. 1985 Mar;46(3 Pt 2):3-6.
The mixed actions of the older tricyclic antidepressants make them generally unsuitable as pharmacologic tools in investigating mechanisms of antidepressant effect. Tricyclics are also relatively dangerous in overdose, and their patient acceptability is limited by marked side effects and cardiotoxicity. The current trend in the development of new antidepressants is to identify pharmacologically active molecules that have selective action. Compounds with a selective effect in blocking serotonin reuptake have recently been developed. Among these, fluoxetine is of substantial theoretical interest because, unlike other serotonin uptake inhibitors, it is rather specific and does not appear to down-regulate beta-receptors. Assessment of the relative efficacy of such compounds should provide insight into the mechanisms of antidepressant effect. Prerequisites of clinical trials for new antidepressants are briefly reviewed.
较老的三环类抗抑郁药的混合作用使其通常不适用于作为研究抗抑郁作用机制的药理学工具。三环类药物过量服用时也相对危险，其副作用明显且具有心脏毒性，限制了患者的接受度。新型抗抑郁药的当前研发趋势是鉴定具有选择性作用的药理活性分子。最近已开发出对阻断5-羟色胺再摄取有选择性作用的化合物。其中，氟西汀具有重大的理论意义，因为与其他5-羟色胺摄取抑制剂不同，它相当特异，且似乎不会下调β受体。评估这类化合物的相对疗效应能深入了解抗抑郁作用的机制。本文简要综述了新型抗抑郁药临床试验的先决条件。
