Category: pharmacological
Aliases: DXM, DM, dex, d-methorphan, Robitussin DM
OTC antitussive acting centrally on the medullary cough reflex. The parent compound is a sigma-1 receptor agonist and weak NMDA receptor antagonist; the principal active metabolite dextrorphan (formed by CYP2D6 O-demethylation) is a much more potent NMDA antagonist and the source of the dissociative effects seen at supratherapeutic doses. CYP2D6 elimination is so dominant that DXM AUC differs ~150-fold between extensive and poor metabolizers — DXM is the canonical CYP2D6 probe substrate in phenotyping protocols. Secondary metabolism is N-demethylation by CYP3A4 to 3-methoxymorphinan. PK (Capon 1996 PMID:8841152 EM cohort, 30 mg PO single): EM median t½ 2.4 h, PM t½ 19.1 h (150-fold AUC difference between phenotypes — the canonical CYP2D6-polymorphism magnitude). EM F low (~11%) due to extensive first-pass CYP2D6; quinidine bumps EM AUC 43-fold (the DMQ combination product for pseudobulbar affect). Authored at EM phenotype default; phenotype-aware PK would split EM vs PM populations.
PO: 2.5h