The Pharmacological Role and Clinical Applications of Antipsychotics’ Active Metabolites: Paliperidone versus Risperidone

Abstract

Some antipsychotic drugs are metabolized in the liver, leading to active metabolites. These metabolites can maintain the effect of the original substrate or display different pharmacokinetic or pharmacodynamic properties, and that can be translated by a different profile of responses and interactions to clinical level. Among these is risperidone, whose active metabolite, 9-OH-risperidone, is known as paliperidone and has been marketed as such. In this review, we analyze the differential pharmacological aspects between risperidone and paliperidone, both from the pharmacokinetic (bioavailability, effect of CYP450 and P-glycoprotein, etc.) and pharmacodynamic perspectives (affinity for dopaminergic and/or serotonergic receptors, speed of dissociation from dopamine receptors, serotonin 5-HT2Areceptor occupancy>D2, etc.) as well as differential electrophysiological profile and neuroprotective role. The pharmacological differences between the two drugs could explain the differential clinical response exhibited by schizophrenic patients treated with both agents, as well as some differences in tolerability profile and drug interactions.