Salvati P, Caravaggi A M, Lamberti E, Monteggia M, Bianchi G
Arzneimittelforschung. 1983;33(8):1098-106.
The effects on blood pressure and heart rate of a new ergoline derivative, 2(R,S)-Cyano-3-(6-methylergolin-8 beta-yl)-propionamide (355/1057), were evaluated in different models of experimental hypertension as well as in normotensive rats, dogs and cats. Its interference with sympathetic neurotransmission was also studied in anaesthetized cats and dogs and in pithed rats. Dose-related hypotensive effects were found after single oral, intraduodenal and intravenous administration. In all the studied experimental models 355/1057 showed a prompt onset of action and a prolonged effect on blood pressure at low doses without substantially modifying heart rate. Some comparative results obtained with other commercially available antihypertensive agents are also reported. One month daily oral administration in SH-rats produced an antihypertensive effect persisting trough the entire experiment with no signs of tachyphylaxis. In anaesthetized dogs 355/1057 inhibited sthe pressor response elicited by bilateral carotid occlusion and in anaesthetized cats it reduced the response of the nictitating membrane elicited by electrical stimulation of both the pre- and post-ganglionic fibers but not by norepinephrine bolus injection.
在不同的实验性高血压模型以及正常血压的大鼠、狗和猫中,评估了一种新的麦角灵衍生物2(R,S)-氰基-3-(6-甲基麦角灵-8β-基)-丙酰胺(355/1057)对血压和心率的影响。还在麻醉的猫和狗以及脊髓切断的大鼠中研究了其对交感神经传递的干扰。单次口服、十二指肠内和静脉给药后发现了与剂量相关的降压作用。在所有研究的实验模型中,355/1057起效迅速,低剂量时对血压的作用持续时间长,且对心率基本无影响。还报告了与其他市售抗高血压药物获得的一些比较结果。在SH大鼠中每日口服给药一个月产生了持续整个实验的降压作用,且无快速耐受性迹象。在麻醉的狗中,355/1057抑制双侧颈动脉闭塞引起的升压反应,在麻醉的猫中,它降低了节前和节后纤维电刺激引起的瞬膜反应,但对去甲肾上腺素推注注射无此作用。