Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330 México D.F., México.
Eur J Pharmacol. 2013 Sep 5;715(1-3):262-9. doi: 10.1016/j.ejphar.2013.05.011. Epub 2013 May 22.
Ergotamine has been used in clinical practice for the acute treatment of migraine for over 90 years. So far, it is known that ergotamine interacts with diverse receptors (including α1/2-adrenoceptors, 5-HT1, 5-HT2 and D2-like receptors) and that produces increases in mean blood pressure which are significantly blocked by yohimbine, a classical α2-adrenoceptor antagonist with a moderate affinity for α1-adrenoceptors. Since α1/2-adrenoceptors mediate vasopressor and vasoconstrictor responses in the cardiovascular system, this study was designed to identify the α-adrenoceptor subtypes (α1A, α1B, α1D, α2A, α2B and α2C) involved in ergotamine-induced vasopressor responses in pithed rats. In male Wistar pithed rats baseline heart rate and blood pressure were recorded. Then, the vasopressor responses to intravenous (i.v.) bolus injections of ergotamine were determined after administration of vehicle or several α1⧸2-adrenoceptor antagonists. I.v. administration of the antagonists prazosin (α1, 0.1-30 µg/kg), rauwolscine (α2, 0.3-300 µg/kg), prazosin (0.1 µg/kg) plus rauwolscine (0.3 µg/kg), 5-methylurapidil (α1A, 100 and 300 µg/kg), L-765,314 (α1B, 100 and 300 µg/kg), BMY 7378 (α1D, 100 and 300 µg/kg), BRL44408 (α2A, 300 and 1000 µg/kg) and JP-1302 (α2C, 300 µg/kg), significantly blocked the vasopressor responses to ergotamine, whereas imiloxan (α2B, 1000 and 3000 µg/kg), JP-1302 (100 µg/kg) or the corresponding vehicles (saline 0.9%, propylene glycol 20% or dimethyl sulfoxide 10%; 1ml/kg) failed to modify the responses to ergotamine. The above results suggest that the vasopressor responses to ergotamine in pithed rats are mainly mediated by α1A-, α1B-, α1D-, α2A- and α2C-adrenoceptors and may explain its adverse/therapeutic effects.
麦角胺在临床实践中已被用于偏头痛的急性治疗超过 90 年。到目前为止，已知麦角胺与多种受体相互作用（包括α1/2-肾上腺素能受体、5-HT1、5-HT2 和 D2 样受体），并导致平均血压升高，而育亨宾是一种经典的α2-肾上腺素能受体拮抗剂，对α1-肾上腺素能受体具有中等亲和力，可显著阻断这种升高。由于α1/2-肾上腺素能受体在心血管系统中介导血管加压和血管收缩反应，因此本研究旨在确定参与麦角胺引起的麻醉大鼠血管加压反应的α-肾上腺素能受体亚型（α1A、α1B、α1D、α2A、α2B 和α2C）。在雄性 Wistar 麻醉大鼠中记录基础心率和血压。然后，在给予载体或几种α1/2-肾上腺素能受体拮抗剂后，测定静脉内（i.v.）推注麦角胺引起的血管加压反应。静脉内给予拮抗剂哌唑嗪（α1，0.1-30μg/kg）、雷沃司琼（α2，0.3-300μg/kg）、哌唑嗪（0.1μg/kg）加雷沃司琼（0.3μg/kg）、5-甲基尿嘧啶（α1A，100 和 300μg/kg）、L-765,314（α1B，100 和 300μg/kg）、BMY 7378（α1D，100 和 300μg/kg）、BRL44408（α2A，300 和 1000μg/kg）和 JP-1302（α2C，300μg/kg）可显著阻断麦角胺引起的血管加压反应，而伊米洛桑（α2B，1000 和 3000μg/kg）、JP-1302（100μg/kg）或相应载体（生理盐水 0.9%、丙二醇 20%或二甲基亚砜 10%；1ml/kg）未能改变麦角胺的反应。上述结果表明，麻醉大鼠麦角胺引起的血管加压反应主要由α1A-、α1B-、α1D-、α2A-和α2C-肾上腺素能受体介导，这可能解释了其不良反应/治疗作用。
