Abstract
A possible mechanism of action of antimigraine drugs such as sumatriptan is inhibition of the trigeminovascular pathway. Sumatriptan's effects might be mediated by 5-HT 1B, 5-HT 1D or 5-HT 1F receptors. To establish the relative importance of these subtypes, we compared the effects of sumatriptan with those of a selective 5-HT 1F receptor agonist (LY 344864) on c- fos protein expression in the trigeminal nucleus caudalis. c- fos expression was induced in urethane-anaesthetized rats by intracisternal capsaicin administration. Sumatriptan and LY 344864 decreased the number of capsaicin-induced c- fos-like immunoreactive cells within trigeminal nucleus caudalis (ID 50=0.04 and 0.6 mg kg −1). The effect of sumatriptan, but not of LY 344864, was prevented by pretreatment with the antagonist SDZ 21-009, which displays high affinity for rat 5-HT 1B receptors. LY 344864 appears to attenuate c- fos-like immunoreactivity via 5-HT 1F receptors, while sumatriptan acts via 5-HT 1B receptors. The fact that activation of 5-HT 1F receptors is sufficient to modulate the activity of the trigeminal system suggests that this receptor may be a target for antimigraine drugs with improved safety profile.
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