Buspirone

For a more detailed discussion of this topic, see Buspirone, Sec. 31.12, p. 3060 in Comprehensive Textbook of Psychiatry, 9th Edition.

Buspirone hydrochloride (BuSpar) is classified as an azapirone and is chemically distinct from other psychotropic agents. It acts on two types of receptors: serotonin (5-HT) and dopamine (D). It has high affinity for the 5-HT_1A serotonin receptor, acting as an agonist or partial agonist, and moderate affinity for the D₂ dopamine receptor, acting as both an agonist and antagonist. The approved indication for this psychotropic drug is for the treatment of generalized anxiety disorder (GAD). It was initially believed to be a better alternative to the benzodiazepine drug group because buspirone does not possess anticonvulsant and muscle relaxant effects. However, it is more currently believed that although the azapirones, including buspirone, are better tolerated than benzodiazepines, combined evidence reveals that they are not more effective.

Pharmacologic Actions

Buspirone is well absorbed from the gastrointestinal tract, but absorption is delayed by food ingestion. Peak plasma levels are achieved 40 to 90 minutes after oral administration. At doses of 10 to 40 mg, single-dose linear pharmacokinetics are observed. Nonlinear pharmacokinetics are observed after multiple doses. Because of its short half-life (2 to 11 hours), buspirone is dosed three times daily. An active metabolite of buspirone, 1-pyrimidinylpiperazine (1-PP), is about 20% less potent than buspirone but is up to 30% more concentrated in the brain than the parent compound. The elimination half-life of 1-PP is 6 hours.

Buspirone acts as an agonist, partial agonist, or antagonist on serotonin 5-HT_1A receptors. Its most pronounced action, as a presynaptic agonist at these receptors, inhibits release of serotonin, with consequent antianxiety effects. Action as an agonist at postsynaptic receptors appears to account for antidepressant activity.

Buspirone has no effect on the γ-aminobutyric acid (GABA)–associated chloride ion channel on that receptor mechanism or the serotonin reuptake transporter, targets of other drugs that are effective in GAD. Buspirone also has activity at 5-HT₂ and dopamine type 2 (D₂) receptors, although the significance of the effects at these receptors is unknown. At D₂

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