Smith R P, Louis C A, Kruszyna R, Kruszyna H
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03756.
Fundam Appl Toxicol. 1991 Jul;17(1):120-7. doi: 10.1016/0272-0590(91)90244-x.
Sodium azide is a chemical of rapidly growing commercial importance with a high acute toxicity and an unknown mechanism of action. Although it has some chemical properties and biological effects in common with cyanide, its lethality does not appear to be due to inhibition of cytochrome oxidase. Unlike cyanide it is a potent vasodilator and inhibitor of platelet aggregation presumably by virtue of its conversion to nitric oxide in vivo and in isolated preparations of blood vessels and thrombocytes. It is not clear whether the high toxicity of azide is due to nitric oxide or to the parent anion. Of a number of possible azide antagonists tested in intact mice only phenobarbital in both anesthetic and subanesthetic doses afforded statistically significant protection against death. Diazepam, phenytoin, and an anesthetic dose of a ketamine/xylazine combination had no effect. Major motor seizures are sometimes seen in human azide poisoning, and these are a regular feature of azide poisoning in laboratory rodents. Solutions of nitric oxide given systemically to mice produced no signs of toxicity, but doses 1,000-fold lower placed in the cerebroventricular system of rats produced brief but violent tonic convulsive episodes. A dose of 0.61 mmol/kg azide as given systemically regularly produced convulsions whereas a dose of 6 mumol/kg given icv produced seizures in rats. The icv convulsive dose of azide was 50-fold larger than the icv dose of nitric oxide. These results suggest that azide lethality is due to enhanced excitatory transmission in the central nervous system perhaps after its conversion to nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)
叠氮化钠是一种商业重要性迅速增长的化学品，具有高急性毒性且作用机制不明。尽管它与氰化物有一些共同的化学性质和生物学效应，但其致死性似乎并非由于抑制细胞色素氧化酶。与氰化物不同，它是一种强效血管扩张剂和血小板聚集抑制剂，可能是因为它在体内以及在离体血管和血小板制剂中转化为一氧化氮。尚不清楚叠氮化物的高毒性是由于一氧化氮还是母体阴离子。在完整小鼠中测试的多种可能的叠氮化物拮抗剂中，只有麻醉剂量和亚麻醉剂量的苯巴比妥能提供具有统计学意义的抗死亡保护作用。地西泮、苯妥英以及氯胺酮/赛拉嗪组合的麻醉剂量均无作用。人类叠氮化物中毒时有时会出现大发作性惊厥，而这是实验室啮齿动物叠氮化物中毒的常见特征。给小鼠全身注射一氧化氮溶液未产生毒性迹象，但剂量比全身注射低1000倍注入大鼠脑室系统会产生短暂但剧烈的强直性惊厥发作。全身注射0.61 mmol/kg叠氮化钠通常会引发惊厥，而脑室内注射6 μmol/kg会使大鼠发作。叠氮化物的脑室内惊厥剂量比一氧化氮的脑室内剂量大50倍。这些结果表明，叠氮化物的致死性可能是由于其转化为一氧化氮后增强了中枢神经系统的兴奋性传递。（摘要截短于250字）
