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

• Main Authors: Matsuzawa Yoshiyasu, Morikawa Tomoko, Makita Koshi, Katayama Yoshifumi
• Format: Article
• Language: English
• Published: SAGE Publishing 2006-03-01
• Series: Molecular Pain
• Online Access: http://www.molecularpain.com/content/2/1/10

<p>Abstract</p> <p>Background</p> <p>Triptans, 5-HT_1B/IDagonists, 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.</p> <p>Results</p> <p>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 μM) reduced the size of I_Bain a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT_1B/1Dantagonist, 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 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/1Dreceptor linked to G_i/opathway.</p> <p>Conclusion</p> <p>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.</p>