desmethylcariprazine

Desmethylcariprazine is an active metabolite of the atypical antipsychotic cariprazine. It is produced in the liver through demethylation of cariprazine by hepatic cytochrome P450 enzymes, with CYP3A4 playing a major role. It is one of the major active metabolites alongside didesmethylcariprazine.

Pharmacology of desmethylcariprazine mirrors much of cariprazine’s activity, acting as a partial agonist at dopamine D2 and D3 receptors, with a tendency toward D3 receptor engagement. This receptor activity is thought to contribute to the overall therapeutic effects of cariprazine, including aspects of mood, motivation, and negative symptoms, though its potency and efficacy differ from the parent compound.

Pharmacokinetics of desmethylcariprazine include formation in vivo with a relatively long elimination profile, resulting in sustained pharmacologic activity beyond the presence of cariprazine itself. The metabolite’s exposure is influenced by dosing, liver function, and concomitant medications that modulate CYP3A4 activity, including inhibitors or inducers.

Clinical implications of this metabolite center on its contribution to overall efficacy and tolerability, as well as the potential for prolonged effects after stopping treatment due to the active metabolite’s persistence. Drug interactions that affect CYP3A4 can alter desmethylcariprazine levels, necessitating consideration in polypharmacy and in patients with hepatic impairment.

See also: cariprazine; didesmethylcariprazine.