Dextromethorphan has been shown to possess the following properties, mainly in binding assays to various receptors of animal tissues. Low Ki values mean strong binding or high affinity; high Ki values mean weak binding to the target or low affinity:
Uncompetitive NMDA receptor (PCP site) antagonist (Ki = 7,253 nM).[18][19][20][21]
σ1 and σ2 sigma receptor agonist (Ki = 205 nM and 11,060 nM, respectively). In a comparative investigation of dimemorfan, dextromethorphan and dextrorphan in mouse cells, dextromethorpan binds with relatively high affinity to Sigma-1 receptors and with very low affinity to Sigma-2 receptors.[18]
α3β4-, α4β2-, and α7-nACh receptor (Ki = in the μM range) antagonist. Dextromethorphan binds to nicotinic receptors in frog eggs (Xenopus oocytes), human embryonic kidney cells and mouse tissue. It inhibits the antinociceptive (pain killing) action of nicotine in the tail-flick test in mice, where mouse tails are exposed to heat, which makes the mouse flick its tail if it feels pain.[22][23][24]
μ-, δ-, and κ-opioid receptor agonist (Ki = 1,280 nM, 11,500 nM, and 7,000 nM, respectively).[25]
SERT and NET blocker (Ki = 23 nM and 240 nM, respectively).[3][25][26][27]
NADPH oxidase inhibitor.[28]
Its affinities for some of the sites listed are relatively very low and are probably insignificant, such as binding to NMDA receptors and opioid receptors, even at high recreational doses.[citation needed] Instead of acting as a direct antagonist of the NMDA receptor itself, it is likely that dextromethorphan functions as a prodrug to its nearly 10-fold more potent metabolite dextrorphan, and this is the true mediator of its dissociative effects.[18] It is not entirely clear what role, if any, (+)-3-methoxymorphinan, dextromethorphan's other major metabolite, plays in its effects.[29]