Villalón C M, De Vries P, Rabelo G, Centurión D, Sánchez-López A, Saxena P
Departamento de Farmacología y Toxicologia, CINVESTAV, I.P.N., México D.F., México.
Br J Pharmacol. 1999 Feb;126(3):585-94. doi: 10.1038/sj.bjp.0702324.
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 alpha-adrenoceptors and several 5-HT1 and 5-HT2 receptor subtypes, this study has analysed the mechanisms involved in the above responses. Intracarotid (i.c.) infusions during 1 min of methysergide (31-310 microg min(-1)), ergotamine (0.56-5.6 microg min(-1)) or DHE (5.6-31 microg 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. The reductions in ECBF by methysergide were abolished and even reversed to increases in animals pre-treated with GR127935 (10 microg kg(-1), i.v.). The reductions in ECBF by ergotamine and DHE remained unchanged in animals pre-treated (i.v.) with prazosin (300 microg kg(-1)), but were partly antagonized in animals pre-treated with either GR127935 (10 or 30 microg kg(-1)) or yohimbine (1000 microg kg(-1)). Pre-treatment with a combination of GR127935 (30 microg kg(-1)) and yohimbine (1000 microg 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. These results suggest that the external carotid vasoconstrictor responses to methysergide primarily involve 5-HT1B/1D receptors, whereas those to ergotamine and DHE are mediated by 5-HT1B/1D receptors as well as alpha2-adrenoceptors.
抗偏头痛药物甲基麦角新碱、麦角胺和双氢麦角胺（DHE）可使戊巴比妥麻醉并进行人工呼吸的去迷走交感神经犬的颈外动脉床产生选择性血管收缩，但所涉及的受体尚未完全明确。由于上述药物对包括α-肾上腺素能受体以及几种5-HT1和5-HT2受体亚型在内的多个结合位点具有亲和力，本研究分析了上述反应所涉及的机制。颈内（i.c.）注射甲基麦角新碱（31 - 310微克·分钟⁻¹）、麦角胺（0.56 - 5.6微克·分钟⁻¹）或DHE（5.6 - 31微克·分钟⁻¹）1分钟，剂量依赖性地使颈外动脉血流量（ECBF）分别降低达46±4%、37±4%和49±5%。血压和心率保持不变。甲基麦角新碱所致的ECBF降低在预先用GR127935（10微克·千克⁻¹，静脉注射）处理的动物中被消除，甚至反转至增加。麦角胺和DHE所致的ECBF降低在用哌唑嗪（300微克·千克⁻¹，静脉注射）预先处理的动物中保持不变，但在用GR127935（10或30微克·千克⁻¹）或育亨宾（1000微克·千克⁻¹）预先处理的动物中部分被拮抗。用GR127935（30微克·千克⁻¹）和育亨宾（1000微克·千克⁻¹）联合预先处理可消除对麦角胺和DHE的反应。上述剂量的拮抗剂在其各自受体处产生选择性拮抗作用。这些结果表明，颈外动脉对甲基麦角新碱的血管收缩反应主要涉及5-HT1B/1D受体，而对麦角胺和DHE的反应则由5-HT1B/1D受体以及α2-肾上腺素能受体介导。
