Inhibitory effect of pranidipine on N-type voltage-dependent Ca2+ channels in mice |
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Authors: | Murakami Manabu Mori Toyoki Nakagawasai Osamu Hagiwara Kunie Sakurada Yumiko Mobarakeh Izadi I Murata Atsunobu Yamadera Fumihiro Miyoshi Ichiro Tan-No Koichi Yanai Kazuhiko Tadano Takeshi Iijima Toshihiko |
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Affiliation: | Department of Pharmacology, Akita University School of Medicine, 1-1-1 Hondoh, Akita 010-8543, Japan. manabumurakami@excite.co.jp |
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Abstract: | We investigated the N-type voltage-dependent calcium channel blocking action of pranidipine, a novel dihydropyridine (DHP) derivative. Pranidipine significantly suppressed KCl-induced intracellular calcium changes ([Ca(2+)](i)) in a dose-dependent fashion in dorsal root ganglion neurons. A patch-clamp investigation revealed a dose-dependent blocking effect on N-type currents. Intrathecal injection of pranidipine significantly shortened the licking time in the late phase of the formalin test, as occurs with cilnidipine and amlodipine, which act on L- and N-type channels. Conversely, nicardipine, which acts exclusively on L-type channels, had no antinociceptive effect. Our results indicate that pranidipine inhibits N-type calcium channels. Furthermore, it exerts an antinociceptive effect, which might be related to an attenuation of synaptic transmission by nociceptive neurons due to the blocking effect of pranidipine on N-type calcium channels in primary nociceptive afferent fibers. |
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