SEROTONIN 5-HT1A AGONISTS - A COMPARATIVE REVIEW

In 1980, buspirone was found to have anxiolytic potential. This finding initiated the development of the azapirones - highly serotonin 5-HT1A agonists. The balance of evidence suggests that the azapirones act as partial agonists postsynaptically, but as full agonists presynaptically in the dorsal raphe. This review focuses mainly on agents for which there are published clinical trial data. Numerous studies have shown that buspirone, gepirone and ipsapirone are as effective as the benzodiazepines in the treatment of generalised anxiety. However, they have a slower onset of action. The azapirones have a completely different adverse reaction profile (dizziness and gastric complaints) compared with the benzodiazepines (sedation, memory loss and withdrawal dependency). Several controlled studies have shown that the azapirones are effective in depression, particularly of the melancholic type. They have an adverse effects profile similar to, but less severe than, the selective serotonin reuptake inhibitors and different to that of the tricyclic antidepressants. Buspirone has not yet proven to be effective in panic disorder. However, gepirone, ipsapirone and other azapirones may be more effective in this disorder. Early studies indicate promising results for buspirone in the treatment of obsessive-compulsive disorder. Clinical trials in alcoholism are equivocal. Further studies of this class of drugs in the treatment of social phobia, post-traumatic stress disorder, premenstrual syndrome, and compulsive and aggressive disorders are in progress. A principle drawback with this class of drug is their short half-life. However, sustained release preparations are being developed.