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.