Use of animal models: toward anxioselective drugs.

The debilitating psychopathology of anxiety neurosis is particularly amenable to relief by pharmacotherapy. While currently available drugs successfully alleviate the distressing symptoms suffered by anxious patients, they also carry potential liabilities which must be considered in their use. Through the use of predictive animal models, researchers hope to elucidate a set of structure-activity relationships through which anxiolytic, and most particularly anxioselective compounds can be rationally designed. Such models should predict side-effect potential as well as efficacy, so that unwanted ancillary effects of potential anxiolytics can be eliminated by appropriate structural modifications. The state of the art in preclinical testing for anxiolytic potential will be discussed with particular emphasis on the need to design test systems capable of detecting anxiolytic activity in diverse, nontraditional chemical series. The contribution of such methodology to the discovery and development of one anxioselective, non-benzodiazepine anxiolytic, buspirone, will be discussed.