Inhibitory effect of pranidipine on N-type voltage-dependent Ca2+ channels in mice.
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.
Department of Pharmacology, Akita University School of Medicine, 1-1-1 Hondoh, Akita 010-8543, Japan. manabumurakami@excite.co.jp
Manabu
M
Murakami
Toyoki
T
Mori
Osamu
O
Nakagawasai
Kunie
K
Hagiwara
Yumiko
Y
Sakurada
Izadi I
II
Mobarakeh
Atsunobu
A
Murata
Fumihiro
F
Yamadera
Ichiro
I
Miyoshi
Koichi
K
Tan-No
Kazuhiko
K
Yanai
Takeshi
T
Tadano
Toshihiko
T
Iijima
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003997:Dicarbethoxydihydrocollidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D005727:Ganglia, Spinal / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D018408:Patch-Clamp Techniques / Q000379:methods; D011189:Potassium Chloride / Q000494:pharmacology; D013997:Time Factors
C105562:2,6-dimethyl-3,5-diethoxycarbonyl-4-carboxyl-1,4-dihydropyridine; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D005557:Formaldehyde; D003997:Dicarbethoxydihydrocollidine; D011189:Potassium Chloride; C065927:cilnidipine; C048161:pranidipine; D002118:Calcium