治疗血吸虫病药:对氨苯氧庚烷的毒性及药理作用

1.对氮苯氧庚烷对小鼠的半数致死量口服为1260毫克/公斤,静脉注射为195毫克/公斤。小白鼠每日口服50-200毫克/公斤,连续两周,因影响食欲致使体重的增加受到抑制,停药后即渐恢复。2.对氨苯氧庚烷对麻醉猫和狗的血压,在静脉注射时有显著而短暂的降低,剂最愈大或注射速度愈快,血压下降亦愈多。3.对于麻醉猫的迴肠及豚鼠离休迴肠,对氨苯氧庚烷均有明显抑制作用。对氨苯氧庚烷并能对抗组织胺、乙醯胆龄及氯化钡对离体豚鼠迴肠的作用。对在体家兔子宫有收缩作用,而对离体子宫则有抑制作用。

THE TOXICITY AND PHARMACOLOGICAL ACTIONS OF P:P'-DIAMINODIPHENOXY HEPTANE,A COMPOUND WITH SCHISTOSOMICIDAL ACTIVITY

The toxicity and pharmacological properties of p:p'-diaminodiphenoxy heptane, a compoud with schistosomicidal activity.are described. The LD₅₀ for mice was 1260 mg./kg. orally and 195 mg./kg.intravenously. Mice became less active and lost appetite after taking the drug orally.Intravenous injection of the compound caused the extremities of mice to paralize for a few seconds.This was followed by clonic convulsion and opisthotonus.Death was due to cardiac arrest. When mice and rats were given small doses of the drug once daily for 14 days,there was no change in blood picture,blood sugar and body temperature. However,the growth of the animals was arrested due to loss of appetite. Oral administation of p:p'-diaminodiphenoxy heptane at a does of 50-100 mg./kg.to dogs caused vomiting in about one and half hours. After abut 24 hours,the pupils of the animals were dilated;light reflex was absent.The dogs did not recover from these effects until after about a month.Intravenous injection of 30 mg./kg.of the drug causdd similar reactions. However,feeding a monkey with 60 mg./kg.through stomach tube did not cause any reaction.This was true even when the monkey was given 20mg./kg.daily for 5 days.The liver function (B.S.P.) and blood N.P.N.levels of the dogs and the monkey fed chronically with the drug were not changed. Intravenous injections of 0.5-2.5mg./kg to anesthetized dogs and cats caused a transient fall of blood pressure.The intestinal movement of the cat was inhibited. Respiration was not affected significantly in the dog.In anesthetized cats,the amplitude of respiration was decreased in most experiments. Addihon of p:p'-diaminodiphenoxy heptane to a bath containing a segment of guinea-pig ileum caused only a slight relaxation of the tissue.However,addition of the drug to a concentration of 1:5000,000-1:50,000 decreased or abolished the reaction of the tissue to acetylcholine,histamine and barium choride.Intravenous injection of 15-20mg./kg.of the drug to rabbits under anesthesia increased the tension of the uterus.