Thioridazine pharmacodynamics: Clinical effects may depend upon drug metabolism

The clinical effects of the phenothiazine antipsychotic, thioridazine (Mellaril), appear to depend in large measure on the biotransformation of the parent drug to biologically active metabolites. This review presents in vitro and in vivo data suggesting that the S-oxidized metabolites of thioridazine have potent antidopaminergic activity. Moreover, in studies with hamsters, a species that metabolizes thioridazine in a manner similar to humans, thioridazine was shown to have potent effects on basal ganglia dopamine. Also, contrary to earlier reports, thioridazine was not found to display a greater effect on mesolimbic versus basal ganglia dopamine in either rats or hamsters. These results suggest that thioridazine may not have 'atypical' actions in humans and may not place patients at a reduced risk for tardive dyskinesia.