Buspirone and related compounds as alternative anxiolytics

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.