Preclinical evidence for the anxiolytic activity of 5‐HT3 receptor antagonists: A review

Abstract

AbstractFrom ancient history to present times, mankind has sought for anxiolytics, and various medications have been found and consequently used, at present culminating in heavy benzodiazepine use. Side‐effects such as dependence and tolerance have always induced the need, and accordingly the search, for new and better treatments. The 5‐HT1A receptor agonists like buspirone are an example of such new therapeutic agents. Whether or not those compounds will indeed be better as well remains to be seen. Recently another new class of putative anxiolytics has been proposed, the 5‐HT3 receptor antagonists. The present article reviews the evidence for anxiolytic activity of this new class of compounds of animal models of anxiety. Compared to the established anxiolytics (benzodiazepines and, to a lesser extent, 5‐HT1A receptor agonists) 5‐HT3 receptor antagonists have a different anxiolytic profile. They are active in a limited number of animal models, they often are very potent and the ratio between therapeutic activity and side‐effects is remarkably large. No evidence for tolerance or rebound effects was found, which makes them an attractive alternative to the benzodiazepines. Preliminary human clinical data are controversial; some investigators have reported positive effects in anxiety, others have not been able to demonstrate this.