The spinal anaesthetic effect of dextromethorphan, dextrorphan, and 3-methoxymorphinan.

Dextromethorphan, an antitussive, has a complex pharmacologic profile and has not been well studied. Our aim was to evaluate whether dextromethorphan and its metabolites, dextrorphan and 3-methoxymorphinan, have a spinal anaesthetic effect. Using a method of spinal blockade in rats, we evaluated the potencies and durations of the effects of dextromethorphan and its metabolites on spinal blockades of motor function and nociception. Bupivacaine was the active control. We found that dextromethorphan and its metabolites produced a dose-related spinal blockade of motor function and nociception. On an ED(50) basis, the ranks of potencies were bupivacaine>dextrorphan>3-methoxymorphinan>dextromethorphan (p<0.05 for the differences). On an equipotent basis, dextrorphan and bupivacaine produced similarly longer nociceptive blockades than did dextromethorphan and 3-methoxymorphinan (p<0.05 for the differences). Co-administration of dextromethorphan or its metabolites with bupivacaine produced an additive effect. In conclusion, intrathecal injections of dextromethorphan or its metabolites, dextrorphan and 3-methoxymorphinan, produced dose-related spinal blockades of motor function and nociception. The suitability of these drugs as clinical spinal anaesthetics is worth further evaluation.