pranidipine and Pain

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.

Topics: Animals; Animals, Newborn; Behavior, Animal; Calcium; Calcium Channel Blockers; Calcium Channels, N-Type; Cells, Cultured; Dicarbethoxydihydrocollidine; Dihydropyridines; Dose-Response Relationship, Drug; Formaldehyde; Ganglia, Spinal; Membrane Potentials; Mice; Neurons; Pain; Pain Measurement; Patch-Clamp Techniques; Potassium Chloride; Time Factors