Buspirone: An Update on a Unique Anxiolytic Agent

Abstract

Buspirone (Buspar) is a azaspirodecanedione anxiolytic agent. Its mechanism of action is extremely complex, but current investigations indicate that its main neuropharmacologic effects are mediated by the 5-HT1A receptors. Other neuroreceptor systems could be involved, as buspirone displays some affinity for DA2 autoreceptors and 5-HT2 receptors. It has been proposed that inhibition of synthesis and release of serotonin result through the combined interactions of neuroreceptors and secondary messenger systems. This action leads to inhibition of the firing rate of 5-HT-containing neurons in the dorsal raphe. From this novel profile, that differs from that of the benzodiazepines, buspirone lacks anticonvulsant and muscle-relaxant properties, and causes only minimal sedation. The drug is rapidly absorbed after oral administration, with a mean bioavailability of 3.9%. After a single oral dose, the mean elimination half-life is 2.1 hours. Buspirone is mainly bound to albumin and alpha 1-acid glycoprotein. It is metabolized to an active metabolite 1-(2-pyrimidinyl) piperazine (1-PP). The mean elimination half-life of 1-PP is 6.1 hours. Buspirone is indicated in the treatment of generalized anxiety disorders. Its efficacy is comparable to the benzodiazepines. Its use in depression and panic disorders requires further investigation. When combined with alcohol or given alone, psychomotor impairment was not detected. Abuse, dependence, and withdrawal symptoms have not been reported. The frequency of adverse effects is low, and the most common effects are headaches, dizziness, nervousness, and lightheadness. Buspirone should be added to drug formularies and could represent a significant addition in psychopharmacology.

Comparison of ketanserin, buspirone and propranolol on arousal, pupil size and autonomic function in healthy volunteers

“…Propranolol is not considered a sedative drug (Currie et al 1988), and there are mixed reports regarding its ability to reduce arousal; impaired psychomotor performance has been reported after single doses (Landauer et al 1979;Salem and McDevitt 1984), but other studies have failed to show such effects (Currie et al 1988;Harmer et al 2001;Ogle et al 1976;Tyrer and Lader 1974). Buspirone is a non-sedative anxiolytic and a partial agonist at the 5-HT1A receptor (Andrade and Nicoll 1987), with some affinity for the dopamine D2 receptor (Jann 1988;Peroutka 1985;Riblet et al 1982). Buspirone has a dose-dependent miotic effect in healthy human subjects (Fanciullacci et al 1995;Phillips et al 1999), but the mechanism remains unclear (Phillips et al 1999).…”

Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study

“…At serotonin 5-HT 1A receptors, aripiprazole is a potent partial agonist (Jordan et al 2001). Partial agonism at 5-HT 1A receptors has been associated with anxiolytic efficacy (Glennon and Dukat 1995), and 5-HT 1A partial agonists have been reported to reduce stress-induced psychosocial deficits in patients with chronic schizophrenia (Jan 1988;Sovner and ParnerSovner 1989). Preclinical studies have demonstrated that aripiprazole is a serotonin 5-HT 2A receptor antagonist (unpublished data).…”

Buspirone and lorazepam in the treatment of generalized anxiety disorder in outpatients

“…Sleep disturbances, which often accompany anxiety disorders, were positively a¤ected by benzodiazepines and their sedative-hypnotic properties, but not by buspirone in most studies (Petracca et al 1990;van Laar et al 1992). Some investigators also reported insomnia to be a side e¤ect of buspirone, which may be attributable to its potential to increase noradrenergic activity (Newton et al 1986;Svensson 1987;Jann 1988). However, other studies demonstrated an improvement of sleep in anxious patients by buspirone, that was put down to the secondary e¤ect of the overall improvement of the anxiety state (Goldberg and Finnerty 1979;Olajide and Lader 1987).…”