Diphenidol inhibited sodium currents and produced spinal anesthesia.
The aim of this study was to evaluate the effect of diphenidol on blocking Na(+) currents and spinal anesthesia. We used the patch-clamp method to examine if diphenidol blocked Na(+) currents. Lidocaine, a common used local anesthesia, was used as control. We also evaluated the potencies and durations of diphenidol and lidocaine on spinal blockades of motor function, proprioception, and nociception in rats. Lidocaine exhibited a concentration- and state-dependent effect on tonic blockade of voltage-gated Na(+) currents in mouse neuroblastoma N2A cells (IC(50) of 8.1 and 138.9 microM at holding potentials of -70 and -100 mV, respectively). Diphenidol was more potent (IC(50) of 0.77 and 62.6 microM at holding potentials of -70 and -100 mV, respectively). However, unlike lidocaine, block of Na(+) currents by diphenidol lacked use-dependence. We also found that diphenidol acted like lidocaine and produced dose-related spinal blockades of motor function, proprioception and nociception. Although diphenidol had similar potencies of spinal anesthesia compared with lidocaine it produced a much longer duration of spinal blockades than lidocaine. Our results demonstrated that intrathecal diphenidol produced a long duration and similar potency on spinal anesthesia compared with lidocaine in rats. The anesthetic effect of diphenidol could be in part due to its blockade of Na(+) currents.
Leung
Yuk-Man
YM
Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.
Wu
Bor-Tsang
BT
Chen
Yu-Chung
YC
Hung
Ching-Hsia
CH
Chen
Yu-Wen
YW
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D008012:Lidocaine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy; D010880:Piperidines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011434:Proprioception / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors
D000779:Anesthetics, Local; D010880:Piperidines; D008012:Lidocaine; D012964:Sodium; C004858:diphenidol