Gras J, Cardelús I, Llenas J, Palacios J M
Pharmacological Development Department, Almirall Prodesfarma, Research Center, Cardener 68-74, 08024-, Barcelona, Spain.
Eur J Pharmacol. 2000 Dec 20;410(1):53-9. doi: 10.1016/s0014-2999(00)00878-5.
Almotriptan is a new 5-HT(1B/1D) receptor agonist effective for treating acute migraine attacks with or without aura. As 3-5% of patients treated with sumatriptan experience chest symptoms thought to be of cardiac origin, we investigated the cardiovascular safety profile of almotriptan in comparison with that of sumatriptan in six animal models. Almotriptan did not modify blood pressure or heart rate in conscious telemetered normotensive Wistar rats (p.o.), in anaesthetised beagle dogs (i.v.), or in conscious beagle dogs (i.v.), and only produced transient increases when administered (s.c.) to telemetered cynomolgus monkeys. Almotriptan did not consistently affect the duration of the electrocardiogram (ECG) intervals in anaesthetised beagle dogs even when the drug was administered into the coronary artery, nor was ECG morphology altered in telemetered cynomolgus monkeys. In contrast, sumatriptan i.v. consistently increased mean blood pressure and heart rate in conscious beagle dogs. Finally, almotriptan did not modify coronary blood flow at a dose of up to 0.3 mg/kg i.v. in conscious beagle dogs. Thus, almotriptan has a favourable cardiovascular safety profile.
阿莫曲坦是一种新型5-HT(1B/1D)受体激动剂，对治疗有无先兆的急性偏头痛发作均有效。由于接受舒马曲坦治疗的患者中有3 - 5%出现被认为源于心脏的胸部症状，我们在六种动物模型中研究了阿莫曲坦与舒马曲坦相比的心血管安全性。阿莫曲坦对清醒遥测血压正常的Wistar大鼠（口服给药）、麻醉的比格犬（静脉注射）或清醒的比格犬（静脉注射）的血压或心率均无影响，仅在对遥测的食蟹猴皮下给药时产生短暂升高。即使将药物注入冠状动脉，阿莫曲坦对麻醉的比格犬的心电图间期持续时间也没有持续影响，对遥测的食蟹猴的心电图形态也没有改变。相比之下，舒马曲坦静脉注射可使清醒比格犬的平均血压和心率持续升高。最后，在清醒比格犬中，静脉注射剂量高达0.3 mg/kg的阿莫曲坦不会改变冠状动脉血流量。因此，阿莫曲坦具有良好的心血管安全性。
