A Comprehensive Monograph on Buspirone (DB00490): Pharmacology, Clinical Utility, and Therapeutic Context

Executive Summary

Buspirone is a novel anxiolytic agent belonging to the azaspirodecanedione class of drugs, distinguished by a pharmacological profile that is fundamentally different from traditional anxiolytics such as benzodiazepines and barbiturates. Its primary mechanism of action is centered on high-affinity partial agonism at serotonin 5-HT1A receptors, with secondary antagonist activity at dopamine D2 receptors. This unique mechanism underpins its clinical characteristics, most notably its efficacy in treating Generalized Anxiety Disorder (GAD) without inducing significant sedation, cognitive impairment, muscle relaxation, or anticonvulsant effects.

A hallmark of buspirone therapy is its delayed onset of anxiolytic action, typically requiring two to four weeks to achieve full therapeutic effect. This delay is a direct consequence of its pharmacodynamic mechanism, which relies on the gradual desensitization of presynaptic 5-HT1A autoreceptors to produce a net enhancement of serotonergic neurotransmission. This characteristic renders buspirone unsuitable for acute or "as-needed" management of anxiety but establishes its utility for chronic GAD.