Ondansetron exhibits the properties of a local anesthetic.

UNLABELLED: The purpose of this study was to determine whether ondansetron (OND) has local anesthetic effects. Using a patch-clamp technique, we showed that OND concentration dependently blocked Na channel currents in freshly isolated neurons of rat brains with a 50% inhibition concentration of 12 microM. The blockade started immediately when OND was applied to the cell body using a fast perfusion system, reached a plateau within 15 s, and recovered to the control level within 30 s after washout of the OND-containing solution. Because this is a known property of local anesthetics, we used the tail-flick technique to verify this effect in vivo in Sprague-Dawley rats (n = 46). OND was injected subcutaneously into the tail at the doses of 0.08, 0.16, and 0.2 mg. The tail-flick latency increased 2 min after OND injection, reaching the plateau within 5 min. This effect was dose-related, lasting from 10 to 25 min. These preliminary data indicate that OND, a selective 5-HT3 receptor antagonist, might serve as a prototype molecule for development of a novel series of local anesthetics. IMPLICATIONS: Ondansetron is a drug used to prevent vomiting, especially in cancer patients after chemotherapy. We found that it also causes numbness when injected under the skin. This new action may contribute to its role in "calming the stomach." We studied the effect of ondansetron on the isolated brain cells of live rats.