青藤碱的药理作用 Ⅱ.毒性及一般药理

青藤碱(sinomenine)对小白鼠口服半数致死量为580±51毫克/公斤;大白鼠一次口服694毫克/公斤无不良反应;犬及猴分别口服45及95毫克/公斤有显著镇静作用及轻度胃肠反应;但静脉给药于犬及猴(5—13.5毫克/公斤)立即出现高度衰弱、血压下降、心率增速、呼吸困难,此种严重反应于一小时许恢复(猴);犬及猴无论口服或静脉给药后,肝、肾功能均无变化;大白鼠亚急性毒性试验表明,该药40及80毫克/公斤/日腹腔注射,连续二周,对动物体重、食欲、血象、内脏病理切片均无明显改变.青藤碱静脉给药可使麻醉兔、犬的血压显著降低,剂量愈大,作用愈显著,其降压作用与M-胆碱反应系统无关,亦无直接扩张血管作用;高浓度抑制离体蛙心的收缩,此外,该药抑制离体肠肌,并对抗毛果芸香碱、组织胺及乙酰胆碱对离体肠肌的作用;本药不延长硫喷妥钠的作用时间.

THE TOXICITY AND GENERAL PHARMACOLOGICAL ACTIONS OF SINOMENINE

In a previous paper, we reported the analgesic and antiphlogistic actions of Sabianine A (an alkaloid identical with Sinomenine); the present paper deals with the toxicity and some general pharmacological actions of the same alkaloid. The essential findings are as follows: The LD₅₀ of Sinomenine in mice administered orally was 580 ± 51 mg/kg. Smaller doses given orally showed sedative effects, but larger ones caused clonic convulsions. Rats receiving Sinomenine 694 mg/kg orally showed no toxic reactions but some sedative effect. Following oral administration of the alkaloid to dogs and monkeys (45 and 95 mg/kg respectively), marked sedation and some gastro-intestinal reaction were observed. In dogs and monkeys single intravenous injections of the alkaloid (5—13.5 mg/kg) caused immediate myasthenia, tachycardia, hypotension, dyspnea, or bradypnea. In the monkeys all these reactions subsided within one hour after appearance. Following subacute administration of the alkaloid to rats, no changes in blood picture and food consumption and no abnormal histological findings were found. Intravenous injection of Sinomenine to anesthetized rabbits (20—50 mg/kg) caused a transient fall of blood pressure. In anesthetized dogs, this hypotensive effect was more marked and prolonged. Repeated intravenous injections caused tachyphylaxis. Neither atropinization nor bilateral vagotomy blocked the hypotensive effect. Sinomenine depressed the contraction of the isolated frog heart at a concentration of 1:1500 and abolished it at 1:750, the alkaloid antagonized the responses of the isolated guinea-pig ileum to both histamine and acetylcholine. The hypnotic action of thiopental in mice was not prolonged by Sinomenine.