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.
Department of Anesthesiology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. mrkwmane@tmd.ac.jp
Tomoko
T
Morikawa
Yoshiyasu
Y
Matsuzawa
Koshi
K
Makita
Yoshifumi
Y
Katayama
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