Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons.
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 microM) reduced the size of IBa 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.


CONCLUSIONS
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.
Morikawa
Tomoko
T
Department of Anesthesiology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. mrkwmane@tmd.ac.jp
Matsuzawa
Yoshiyasu
Y
Makita
Koshi
K
Katayama
Yoshifumi
Y
D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D019204:GTP-Binding Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D023303:Oxazolidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects*; D014276:Trigeminal Nerve / Q000187:drug effects*; D014363:Tryptamines / Q000494:pharmacology*
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D023303:Oxazolidinones; D014363:Tryptamines; D001464:Barium; C089750:zolmitriptan; D019204:GTP-Binding Proteins; D002118:Calcium