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Ondansetron exhibits the properties of a local anesthetic
1Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, Newark 07103-2714, USA. ye@umdnj.edu
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.
Insights
Ondansetron (OND), a medication for nausea, demonstrates local anesthetic properties by blocking sodium channels. This finding suggests OND could be a basis for developing new numbing agents.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Ondansetron (OND) is a selective 5-HT3 receptor antagonist primarily used to manage nausea and vomiting.
- The potential for non-traditional pharmacological actions of established drugs is an area of ongoing research.
Purpose of the Study:
- To investigate the potential local anesthetic effects of ondansetron (OND).
- To explore the mechanism of OND's action on neuronal sodium channels.
Main Methods:
- Patch-clamp electrophysiology was used to assess OND's effect on Na+ channel currents in isolated rat neurons.
- The tail-flick test in Sprague-Dawley rats was employed to evaluate OND's analgesic and local anesthetic effects in vivo.
Main Results:
- Ondansetron (OND) exhibited dose-dependent blockade of Na+ channel currents in rat neurons, with an IC50 of 12 microM.
- In vivo studies showed that subcutaneous OND injection into rat tails produced a dose-related increase in tail-flick latency, indicating local anesthetic activity.
- The observed effects were rapid in onset and reversible upon washout.
Conclusions:
- Ondansetron (OND) possesses local anesthetic properties, evidenced by its ability to block neuronal sodium channels and produce analgesia in vivo.
- These findings suggest that OND could serve as a lead compound for the development of novel local anesthetics.
- The local anesthetic action may contribute to the gastrointestinal "calming" effects attributed to OND.