D D Mitsikostas, M Sanchez del Rio, M A Moskowitz, C Waeber
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA.
European journal of pharmacology 1999 Mar 26A possible mechanism of action of antimigraine drugs such as sumatriptan is inhibition of the trigeminovascular pathway. Sumatriptan's effects might be mediated by 5-HT1B, 5-HT1D or 5-HT1F receptors. To establish the relative importance of these subtypes, we compared the effects of sumatriptan with those of a selective 5-HT1F 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 (ID50 = 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-HT1B receptors. LY 344864 appears to attenuate c-fos-like immunoreactivity via 5-HT1F receptors, while sumatriptan acts via 5-HT1B receptors. The fact that activation of 5-HT1F 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.
D D Mitsikostas, M Sanchez del Rio, M A Moskowitz, C Waeber. Both 5-HT1B and 5-HT1F receptors modulate c-fos expression within rat trigeminal nucleus caudalis. European journal of pharmacology. 1999 Mar 26;369(3):271-7
PMID: 10225363
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