Gras J, Llupià J, Llenas J, Palacios J M
Department of Pharmacological Development, Almirall Prodesfarma, Research Center, Cardener 68-74, 08024-Barcelona, Spain.
Arzneimittelforschung. 2001 Sep;51(9):726-32. doi: 10.1055/s-0031-1300106.
Almotriptan (3-[2-(dimethylamino) ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl)-1H-indole, CAS 154323-57-6) is a new 5-HT1B/1D agonist whose clinical efficacy has been demonstrated in Phase III clinical trials. This study aimed to evaluate the safety of almotriptan with respect to the central nervous system, renal function and respiratory dynamics using preclinical animal models. The results indicate that almotriptan does not cross the blood-brain barrier, since no effects on/interaction with spontaneous locomotor activity, hexobarbital-induced sleeping time, caffeine-induced increase of spontaneous locomotor activity, or hypothermia (caused by stimulation of central 5-HT1D receptors) was observed following treatment. Almotriptan had a mild antiemetic effect and a slight, transient diuretic effect in dogs, although the latter effect is probably of no clinical relevance. In addition, no effect on the respiratory system of conscious guinea pigs was observed following almotriptan treatment. These results indicate that almotriptan has a favourable safety profile with respect to the central nervous, renal and respiratory systems.
阿莫曲坦（3-[2-(二甲基氨基)乙基]-5-(吡咯烷-1-基磺酰基甲基)-1H-吲哚，CAS 154323-57-6）是一种新型5-HT1B/1D激动剂，其临床疗效已在III期临床试验中得到证实。本研究旨在使用临床前动物模型评估阿莫曲坦在中枢神经系统、肾功能和呼吸动力学方面的安全性。结果表明，阿莫曲坦不会穿过血脑屏障，因为在治疗后未观察到对自发运动活动、己巴比妥诱导的睡眠时间、咖啡因诱导的自发运动活动增加或体温过低（由中枢5-HT1D受体刺激引起）有任何影响/相互作用。阿莫曲坦在犬中有轻微的止吐作用和轻微、短暂的利尿作用，尽管后一种作用可能无临床意义。此外，在阿莫曲坦治疗后，未观察到对清醒豚鼠呼吸系统有任何影响。这些结果表明，阿莫曲坦在中枢神经、肾脏和呼吸系统方面具有良好的安全性。
