BACKGROUND: Dextromethorphan blocks sodium channels, the site of action of local anesthetics. In this study we evaluated whether dextromethorphan has a local anesthetic effect.
METHODS: We administered dextromethorphan and its active metabolite— dextrorphan, and lidocaine subcutaneously to rats and tested them for cutaneous anesthesia. Drug–drug interactions and systemic safety indices (LD50s/ED50s) were also evaluated.
RESULTS: Dextromethorphan and dextrorphan had a local anesthetic effect after cutaneous infiltration. The ranking of potencies was dextromethorphan > dextrorphan > lidocaine (P < 0.01 for each comparison). A combination of dextromethorphan or dextrorphan with lidocaine produced an additive effect. Dextromethorphan and dextrorphan had 2.4- and 1.9-fold higher system safety indices than did lidocaine.
CONCLUSION: Dextromethorphan and dextrorphan were more potent local anesthetics than lidocaine, but with higher systemic safety indices. Coadministration of dextromethorphan or dextrorphan with lidocaine produced an additive effect.