Dextromethorphan has been found to possess the following actions (<1 μM) using rat tissues:
* Uncompetitive antagonist of the NMDA receptor via the MK-801/ site
*  and  blocker (cf. serotonin–norepinephrine reuptake inhibitor)
* Sigma σ receptor agonist
* Negative allosteric modulator of nicotinic acetylcholine receptors
* Ligand of the serotonin 5-HT, histamine H, α-adrenergic, and muscarinic acetylcholine receptors
Dextromethorphan is a prodrug of dextrorphan, which is the actual mediator of most of its dissociative effects through acting as a more potent NMDA receptor antagonist than dextromethorphan itself. What role, if any, (+)-3-methoxymorphinan, dextromethorphan's other major metabolite, plays in its effects is not entirely clear.