• Yuk-Man Leung, Jann-Inn Tzeng, Chi-Li Gong, Yu-Wen Wang, Yu-Wen Chen, and Jhi-Joung Wang.
• Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.
• Eur. J. Pharmacol. 2015 Jan 5;746:213-20.

AbstractThe underlying mechanisms for the action of caramiphen used in local anesthesia are not well understood. The purpose of this study was to evaluate the block of caramiphen on voltage-gated Na⁺ channels and in spinal anesthesia. We investigated the effect of caramiphen on voltage-gated sodium channels in differentiated neuronal NG108-15 cells as well as on rat motor function, proprioception, and pain behavior (when administered intrathecally). In in vitro experiments, lidocaine produced concentration- and state-dependent effects on tonic block of voltage-gated Na⁺ currents (IC₅₀ of 66.2 and 212.9 µM at holding potentials of -70 and -100 mV, respectively). Caramiphen exhibited a milder state-dependence of block (IC₅₀ of 52.1 and 99.5 µM at holding potentials of -70 and -100 mV, respectively). Lidocaine showed a much stronger frequency-dependence of block than caramiphen: with high frequency stimulation (3.33 Hz), 50 µM caramiphen elicited an additional 20% blockade, whereas the same concentration of lidocaine produced 50% more block. In in vivo experiments, caramiphen with a more sensory-selective action over motor blockade was more potent than lidocaine (P<0.05) in spinal anesthesia. On an equipotent basis (25% effective dose (ED₂₅), ED₅₀, and ED₇₅), the duration of caramiphen at producing spinal anesthesia was longer than that of lidocaine (P<0.01). Our data revealed that caramiphen had a more potent, prolonged spinal blockade with a more sensory/nociceptive-selective action over motor blockade in comparison with lidocaine. Spinal anesthesia with caramiphen could be through the suppression of voltage-gated Na⁺ currents.Copyright © 2014 Elsevier B.V. All rights reserved.

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