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预防梭曼中毒的新型模拟器:储存部位的结构特异性

New simulators in the prophylaxis against soman poisoning: structural specificity for the depot site(s).

作者信息

Van Helden H P, Benschop H P, Wolthuis O L

出版信息

J Pharm Pharmacol. 1984 May;36(5):305-8. doi: 10.1111/j.2042-7158.1984.tb04379.x.

Abstract

The oxime HI-6 is effective as an antidote in the soman poisoned (6-8LD50) rat, however, successfully treated animals subsequently show a gradual relapse of signs of poisoning and eventually die after several hours. The relapse is caused by the reappearance of soman at specific sites, after having been elsewhere in the body. Diaphragms isolated from poisoned rats successfully treated with HI-6 also showed a 'secondary' relapse of poisoning. Eight compounds chemically related to soman-soman-simulators--have been tested as prophylactic agents, for their potency in preventing the reappearance of poisoning. The idea was that such compounds may block the non-synaptic binding sites for soman. Three of the 8 compounds proved very effective, which gave some insight into the chemical structure needed for this type of prophylactic action.

摘要

肟HI-6对梭曼中毒(6-8倍半数致死剂量)的大鼠有解毒作用,然而,成功治疗后的动物随后会逐渐出现中毒症状复发,最终在数小时后死亡。复发是由于梭曼在体内其他部位后,又在特定部位重新出现所致。从经HI-6成功治疗的中毒大鼠分离出的膈肌也出现了中毒的“二次”复发。已测试了8种与梭曼化学相关的化合物——梭曼模拟物——作为预防剂,看它们预防中毒症状复发的效力。其想法是这类化合物可能会阻断梭曼的非突触结合位点。8种化合物中有3种证明非常有效,这为这种预防作用所需化学结构提供了一些见解。

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