title: Caramiphen-induced block of sodium currents and spinal anesthesia.
abstract: The 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.
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Yuk-Man
authors.initials: YM
authors.lastname: Leung
authors.affiliation: Department of Anesthesiology, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan; Department of Food Sciences and Technology, Chia Nan University of Pharmacy and Science, Jen-Te, Tainan City, Taiwan.
authors.forename: Jann-Inn
authors.initials: JI
authors.lastname: Tzeng
authors.affiliation: Department of Physiology, China Medical University, Taichung, Taiwan.
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Gong
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Department of Physical Therapy, China Medical University, Taichung, Taiwan; Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan. Electronic address: cywhwok@mail.cmu.edu.tw.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan.
authors.forename: Jhi-Joung
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000775:Anesthesia, Spinal; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D003517:Cyclopentanes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D059225:Nociception / Q000187:drug effects; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D061567:Voltage-Gated Sodium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000779:Anesthetics, Local; D003517:Cyclopentanes; D009419:Nerve Tissue Proteins; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; C004519:caramiphen
keywords: Caramiphen; Duration; Intrathecal; Lidocaine; Sodium currents; Spinal block