Nisoxetine blocks sodium currents and elicits spinal anesthesia in rats.

Abstract

BACKGROUND:

Although nisoxetine has been shown to elicit infiltrative cutaneous local anesthesia, the inhibition of voltage-gated Na(+) channels by nisoxetine has not been reported. The aim of this study was to evaluate the effect of nisoxetine on Na(+) currents and its efficacy on spinal anesthesia.

METHODS:

In in vitro studies, the voltage-clamp method was employed to examine whether nisoxetine blocked Na(+) currents in mouse neuroblastoma N2A cells.

RESULTS:

Mepivacaine showed concentration- and state-dependent effect on tonic blockade of voltage-gated Na(+) currents (IC50 of 3.7 and 74.2 μM at holding potentials of -70 and -100 mV, respectively). Nisoxetine was more potent (IC50 of 1.6 and 28.6 μM at holding potentials of -70 and -100 mV, respectively). In in vivo studies, after rats were intrathecally injected with nisoxetine and mepivacaine, the dose-response curves were constructed. Nisoxetine acted like local anesthetic mepivacaine and induced spinal anesthesia with a more sensory-selective action (p < 0.05) over motor blockade in a dose-related fashion. Intrathecal 5% dextrose (vehicle) produced no spinal anesthesia. On the 50% effective dose (ED50) basis, nisoxetine elicited more potent spinal anesthesia than did mepivacaine (p < 0.05).

CONCLUSIONS:

Our results showed that nisoxetine displayed a more potent and prolonged spinal anesthesia with a more sensory/nociceptive-selective action over motor blockade, compared with mepivacaine. The local anesthetic effect of nisoxetine could be probably due to the suppression of Na(+) currents.

• Authors: Yuk-Man Leung, Chin-Chen Chu, Chang-Shin Kuo, Yu-Wen Chen, Jhi-Joung Wang
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 65 Issue 2 Pg. 350-7 ( 2013) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 23744419 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Local
• Voltage-Gated Sodium Channel Blockers
• Voltage-Gated Sodium Channels
• Fluoxetine
• nisoxetine
• Mepivacaine

Topics

• Anesthesia, Spinal (methods)
• Anesthetics, Local (administration & dosage, pharmacology)
• Animals
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Fluoxetine (administration & dosage, analogs & derivatives, pharmacology)
• Inhibitory Concentration 50
• Injections, Spinal
• Male
• Mepivacaine (administration & dosage, pharmacology)
• Mice
• Neuroblastoma (metabolism)
• Patch-Clamp Techniques
• Rats
• Rats, Sprague-Dawley
• Voltage-Gated Sodium Channel Blockers (administration & dosage, pharmacology)
• Voltage-Gated Sodium Channels (drug effects, metabolism)