Buspirone: chemical profile of a new class of anxioselective agents

Buspirone is a lipophilic, dibasic heterocyclic with no structural resemblance to other anxiolytic or antipsychotic agents. Neurochemical binding studies suggest that buspirone has both dopamine agonist and antagonist properties. Structural comparisons with (+)-butaclamol indicate that buspirone possesses features required for binding at the postsynaptic dopamine receptor site. This is consonant with the drug's biologic properties, but does not define a mechanism for its anxioselective action. The transient antipsychotic effect associated with peak blood levels of buspirone in rats was consistent with such an effect, predicted by [3H]spiperone binding studies. The low (20 mg) anxioselective dose, acting in concert with extensive metabolism in humans, produces low blood levels of the parent drug, suggesting that buspirone's effect is exerted through interactions with a high-affinity, low-threshold receptor system.