dextromethorphan

Dextromethorphan, commonly abbreviated as DXM, is an over-the-counter medication used as a cough suppressant (antitussive). It is the dextrorotatory enantiomer of a morphinan derivative and is distinct from opioid analgesics in typical clinical use. In standard formulations, it is often combined with other cough and cold ingredients such as guaifenesin or phenylephrine. At approved doses, it does not provide pain relief or significant addiction potential.

Pharmacology: Dextromethorphan acts primarily by depressing the cough reflex in the medulla. At higher doses, it acts as a noncompetitive antagonist of the NMDA receptor and interacts with sigma-1 receptors. It also exerts weak effects on monoamine reuptake. The pharmacologically active metabolite dextrorphan contributes to NMDA antagonism and to some of the dissociative effects observed at high doses.

Pharmacokinetics: When taken orally, DXM is absorbed and undergoes extensive first-pass metabolism in the liver. Hepatic CYP2D6 converts it to dextrorphan (DXO), which also has antitussive activity. Genetic variation in CYP2D6 causes substantial interindividual differences in effects. Both DXM and DXO are excreted in urine; the elimination half-life is typically a few hours, varying with metabolism.

Safety and regulation: Dextromethorphan is generally safe at recommended doses, but common side effects include drowsiness, dizziness, and nausea. Overdose or high-dose misuse can cause confusion, agitation, ataxia, seizures, and, in extreme cases, coma. Serotonergic interactions with MAO inhibitors or certain antidepressants can raise the risk of serotonin syndrome. It can interact with alcohol and other sedatives. It is widely available OTC in many countries, though some jurisdictions impose age or quantity restrictions.