Dextromethorphan: Pharmacology, clinical uses and health effects

Dextromethorphan (DM) is an over-the-counter antitussive drug that is also used as one of the active ingredients in many cold and cough medicines. In recent years, DM has also been used in other medicine, ranging from pain relief (as either the primary analgesic or an opioid potentiater) over psychological applications to the treatment of addiction. Pharmacodynamics of DM are gradually discovered with the elucidation of the following properties, including uncompetitive NMDA receptor antagonist, s1 and s2 sigma receptor agonists, a3ß4-nACh receptor antagonist, and others. DM is transformed to its primary and active metabolite dextrorphan predominantly via the metabolic enzyme cytochrome P450 (CYP) 2D6. Hence, DM is the first-choice substrate for CYP2D6 phenotyping because it is relatively safe and possesses many favorable pharmacokinetic characteristics for a marker substrate.