Olivier B, van Wijngaarden I, Soudijn W
Department of Psychopharmacology, Faculty of Pharmacy, Rudolf Magnus Institute for Neurosciences, University of Utrecht, Utrecht, The Netherlands.
Eur Neuropsychopharmacol. 2000 Mar;10(2):77-95. doi: 10.1016/s0924-977x(99)00065-6.
The present paper reviews the evidence for anxiolytic activity of 5-HT(3) receptor antagonists in animal models of anxiety and in clinical trials in humans. Compared to the established anxiolytics (benzodiazepine receptor agonists and, to a lesser extent, 5-HT(1A) receptor agonists) 5-HT(3) receptor antagonists display a different anxiolytic profile. They are anxiolytic in a limited number of animal anxiety models. If active, they often are very potent and display bell-shaped dose response curves, whereas the ratio between therapeutic activity and side effects appears remarkably large. 5-HT(3) receptor antagonists remain active after chronic dosing and no indications for tolerance, dependence or rebound effects were found, which seems to make these drugs an attractive alternative to the benzodiazepines. However, the large body of animal data indicating a complete lack of psychotropic activity of 5-HT(3) receptor antagonists weakens the prediction of anxiolytic activity in these drugs. Human data are also controversial; some investigators have reported positive effects in anxiety disorders (panic disorder, GAD), others did not. It can be concluded that 5-HT(3) receptor antagonists do not represent a breakthrough in the treatment of various anxiety disorders, as initially suggested.
本文综述了5-羟色胺（5-HT）3受体拮抗剂在动物焦虑模型及人类临床试验中的抗焦虑活性证据。与已确立的抗焦虑药（苯二氮䓬受体激动剂，以及在较小程度上的5-HT1A受体激动剂）相比，5-HT3受体拮抗剂表现出不同的抗焦虑特性。它们仅在有限数量的动物焦虑模型中具有抗焦虑作用。如果有活性，它们通常效力很强，并呈现钟形剂量反应曲线，而其治疗活性与副作用之间的比率似乎非常大。5-HT3受体拮抗剂在长期给药后仍保持活性，未发现耐受性、依赖性或反跳效应的迹象，这似乎使这些药物成为苯二氮䓬类药物有吸引力的替代品。然而，大量动物数据表明5-HT3受体拮抗剂完全缺乏精神活性，这削弱了对这些药物抗焦虑活性的预测。人体数据也存在争议；一些研究人员报告了在焦虑症（惊恐障碍、广泛性焦虑症）中的积极效果，另一些则没有。可以得出结论，5-HT3受体拮抗剂并不像最初所认为的那样，在各种焦虑症的治疗中代表着一项突破。
