Abstract
Dextromethorphan blocks sodium channels, the site of action of local anesthetics. In this study we evaluated whether dextromethorphan has a local anesthetic effect. 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. 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. 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.
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