Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: Role of 5-HT(1B/1D) receptors and α2-adrenoceptors

Abstract

1. The antimigraine drugs methysergide, ergotamine and dihydroergotamine (DHE) produce selective vasoconstriction in the external carotid bed of vagosympathectomized dogs anaesthetized with pentobarbital and artificially respired, but the receptors involved have not yet been completely characterized. Since the above drugs display affinity for several binding sites, including α-adrenoceptors and several 5-HT1 and 5-HT2 receptor subtypes, this study has analysed the mechanisms involved in the above responses. 2. Intracarotid (i.c.) infusions during 1 min of methysergide (31-310 μg min-1), ergotamine (0.56-5.6 μg min-1) or DHE (5.6-31 μg min-1) dose-dependently reduced external carotid blood flow (ECBF) by up to 46 ± 4, 37 ± 4 and 49 ± 5%, respectively. Blood pressure and heart rate remained unchanged. 3. The reductions in ECBF by methysergide were abolished and even reversed to increases in animals pre-treated with GR127935 (10 μg kg-1, i.v.). 4. The reductions in ECBF by ergotamine and DHE remained unchanged in animals pre-treated (i.v.) with prazosin (300 μg kg-1), but were partly antagonized in animals pre-treated with either GR127935 (10 or 30 μg kg-1) or yohimbine (1000 μg kg-1). Pre-treatment with a combination of GR127935 (30 μg kg-1) and yohimbine (1000 μg kg-1) abolished the responses to both ergotamine and DHE. The above doses of antagonists were shown to produce selective antagonism at their respective receptors. 5. These results suggest that the external carotid vasoconstrictor responses to methysergide primarily involve 5-HT(1B/1D) receptors, whereas those to ergotamine and DHE are mediated by 5-HT(1B/1D) receptors as well as α2-adrenoceptors.