Dextromethorphan (DXM) is a cough suppressant used in many cough and cold medicines. It affects serotonin, norepinephrine, NMDA, and sigma-1 receptors in the brain, all of which have been implicated in the pathophysiology of depression. In 2022, the FDA approved the combination dextromethorphan/bupropion to serve as a rapid acting antidepressant in patients with major depressive disorder.
It is in the morphinan class of medications with sedative, dissociative, and stimulant properties (at lower doses). Dextromethorphan does not have a significant affinity for the mu-opioid receptor activity typical of morphinan compounds and exerts its therapeutic effects through several other receptors. In its pure form, dextromethorphan occurs as a white powder.
When exceeding approved dosages, dextromethorphan acts as a dissociative hallucinogen. It has multiple mechanisms of action, including actions as a nonselective serotonin reuptake inhibitor and a sigma-1 receptor agonist. Dextromethorphan and its major metabolite, dextrorphan, also block the NMDA receptor at high doses, which produces effects similar to other dissociative anesthetics such as ketamine, nitrous oxide, and phencyclidine.
It was patented in 1949 and approved for medical use in 1953.