Morphinan Dissociatives

Morphinans by skeleton, dissociatives by effect — the clearest case on this site for keeping structure and effect on separate axes. DXM and dextrorphan are dextrorotatory forms of the morphinan ring: they lose the μ-opioid activity the levorotatory forms have and antagonise NMDA instead. Levomethorphan, filed here as the counterpart, is the levorotatory form and is an opioid. Which enantiomer you have decides which drug it is.

DXM is O-demethylated to dextrorphan by CYP2D6, so the effect depends on an enzyme whose activity varies genetically and which several antidepressants and bupropion inhibit — the same dose is not the same exposure in two people, or in one person who has started a new prescription. DXM also inhibits serotonin reuptake, so serotonin syndrome is a real combination risk, and the cough products it is sold in often contain paracetamol or antihistamines that poison first.