Preclinical pharmacodynamic and pharmacokinetic characterization of the major metabolites of cariprazine.

ABSTRACT:

Introduction

Cariprazine, a dopamine D₃-preferring D₃/D₂ receptor partial agonist and serotonin 5-HT_1A receptor partial agonist, has two major human metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR). The metabolite pharmacology was profiled to understand the contribution to cariprazine efficacy.

Methods

In vitro receptor binding and functional assays, electrophysiology, animal models, microdialysis, and kinetic-metabolism approaches were used to characterize the pharmacology of DCAR and DDCAR.

Results

Similar to cariprazine, both metabolites showed high affinity for human D₃, D_2L, 5-HT_1A, 5-HT_2A, and 5-HT_2B receptors, albeit with higher select

SUBMITTER: Kiss B 

PROVIDER: S-EPMC6754336 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature