Nisoxetine blocks sodium currents and elicits spinal anesthesia in rats

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 -100mv,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. copyright © 2013 by institute of pharmacology.