Dopamine and mania: behavioral and biochemical effects of the dopamine receptor blocker pimozide

Although recent data suggest that pimozide has effects at other neurotransmitter receptor sites, it is one of the more specific neuroleptics in its effects on dopamine receptors. We report that in manic patients pimozide produces substantial clinical improvement with a magnitude and time course similar to that observed with the more routinely used phenothiazines chlorpromazine and thioridazine. Pimozide did not significantly increase probenecid-induced accumulations of the dopamine metabolite homovanillic acid (HVA) compared to pretreatment values. Higher HVA values were observed in manic than in nonmanic patients, however. These clinical and biochemical data add to a growing body of indirect evidence that a dopaminergic alteration may be associated with some components of the manic syndrome.