Molecular basis of buspirone's anxiolytic action

Abstract

Buspirone has been available in the United States for over four years for the treatment of anxiety. It was anticipated this drug would offer certain advantages over the established benzodiazepines. In contrast to diazepam, early studies found no evidence for the interaction of buspirone with GABAergic mechanisms. Behavioural, electrophysiological and receptor binding experiments gradually led to the idea that buspirone owes much of its anxiolytic activity to its ability to attenuate central 5-hydroxytryptamine neurotransmission. Specifically, it appears to act as an agonist at presynaptic 5-HT1A receptors, particularly in the raphe nuclei. Although buspirone also shows an affinity for dopamine D2 receptors, where it seems to behave as an antagonist, there is much doubt that this effect is related to its anxiolytic action. Even though buspirone and the benzodiazepines do not obviously share a common mode of action, the possibility is discussed that there is an underlying common mechanism of responsible for their antianxiety effects.