Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5-HT1B/1D receptors and alpha(2)-adrenoceptors

1 The antimigraine drugs methysergide, ergotamine and dihydroergotamine (DH E) produce selective vasoconstriction in the external carotid bed of vagosy mpathectomized dogs anaesthetized with pentobarbital and artificially respi red, but the receptors involved have not yet been completely characterized. Since the above drugs display affinity for several binding sites, includin g alpha-adrenoceptors and several 5-HT1 and 5-HT2 receptor subtypes, this s tudy has analysed the mechanisms involved in the above responses. 2 Intracarotid (i.c.) infusions during 1 min of methysergide (31 - 310 mu g min(-1)), ergotamine (0.56-5.6 mu g min(-1)) or DHE (5.6-31 mu g 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 t o increases in animals pre-treated with GR127935 (10 mu g kg(-1), i.v.). 4 The reductions in ECBF by ergotamine and DHE remained unchanged in animal s pre-treated (i.v.) with prazosin (300 mu g kg(-1)), but were partly antag onized in animals pre-treated with either GR127935 (10 or 30 mu g kg(-1)) o r yohimbine (1000 mu g kg(-1)). Pre-treatment with a combination of GR12793 5 (30 mu g kg(-1)) and yohimbine (1000 mu g kg(-1)) abolished the responses to both ergotamine and DHE. The above doses of antagonists were shown to p roduce selective antagonism at their respective receptors. 5 These results suggest that the external carotid vasoconstrictor responses to methysergide primarily involve 5-HT1B/1D receptors, whereas those to er gotamine and DHE are mediated by 5-HT1B/1D receptors as well as alpha(2)-ad renoceptors.