Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons

Background: Triptans, 5-HT1B/1D agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons ( TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated ( HVA) Ca2+ channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca2+ channels are not yet documented. Results: In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca2+ channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba2+ currents (I-Ba) passing through Ca2+ channels. Zolmitriptan (0.1 - 100 mu M) reduced the size of I-Ba in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT1B/1D antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/ Q-type Ca2+ channel blockers inhibited the inhibitory action of zolmitriptan on I-Ba, compared to Nand L-type blockers, and R-type blocker did, compared to L-type blocker, respectively ( p < 0.05). All of the present results indicated that zolmitriptan inhibited HVA P/Q- and possibly R-type channels by activating the 5-HT1B/1D receptor linked to G(i/o) pathway. Conclusion: It is concluded that this zolmitriptan inhibition of HVA Ca2+ channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan.