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Background  Triptans, 5-HT 1B/ID  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) Ca 2+  channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca 2+  channels are not yet documented.    Results  In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca 2+  channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba 2+  currents (I Ba ) passing through Ca 2+  channels. Zolmitriptan (0.1–100 μM) reduced the size of I Ba  in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT 1B/1D  antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/Q-type Ca 2+  channel blockers inhibited the inhibitory action of zolmitriptan on I Ba , compared to N- and 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-HT 1B/1D  receptor linked to G i/o  pathway.    Conclusion  It is concluded that this zolmitriptan inhibition of HVA Ca 2+  channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan.

molecular pain

Antimigraine Drug, Zolmitriptan, Inhibits High-Voltage Activated Calcium Currents in a Population of Acutely Dissociated Rat Trigeminal Sensory Neurons