オキシム剤のパラチオン中毒に対する解毒効果

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書誌事項

タイトル別名
  • EFFECT OF PYRIDINE-ALDOXIMES, PAM AND TMB-4 ON ORGANOPHOSPHATE POISONING
  • オキシムザイ ノ パラチオン チュウドク ニ タイスル ゲドク コウカ
  • オキムシザイ ノ パラチオン チュウドク ニ タイスル ゲドク コウカ

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説明

Since the discovery of PAM (pyridin-2-aldoxime methiodide) by Wilson in 1955, its effectiveness on restoring the acetocholinesterase (AChE) in vitro and in vivo and its capacity for saving animals in organophosphate poisoning have been well established by many workers. However, later investigations on the effect of PAM against the War gas Sarin revealed unsatisfactory results and newer allied oximes were synthesized to overcome these difficulties. One of them, TMB-4 (bis-pyridine-4-aldoxime trimethylen dibromide), was reported to be the most potent agent by American and British workers. The author conducted comparative studies on the effect of PAM and TMB-4 in vitro and in vivo. In vitro experiments: With human red cells, which had been inhibited by paraoxon and washed for the removal of the inhibitor, reactivations of AChE by PAM and TMB-4 were found to be not far different. With mice brain homogenate, TMB-4 was more potent than PAM, especially when the inhibition was severe. By the use of TMB-4 the maximum reactivation level of AChE was higher as well as the concentration necessary for bringing to the equal level of restoration was far lower than that of PAM. Animal experiments: However, the intraperitoneal toxicity for mice was higher in TMB-4 than PAM, LD50 being 92 and 257 mg/kg respectively. Tests how the oximes could raise the LD50 of parathion for mice revealed that 100 mg/kg of PAM when injected intraperitoneally raised it by 2.5 times, whereas the same amounts of TMB-4 raised it by 3.5 fold. Thus, the overal potency ratio of TMB-4 to PAM was 1.5. In TEPP poisoning, this potency ratio was higher, beging 2.24. In rabbits poisoned with parathion, the blood ChE began to decrease down to the dangerous zone in several hour as after the injection of PAM, while one shot of TMB-4 injection could maintain higher levels of AChE even after six hours. Severely poisoned rabbits were rescued by TMB-4 while PAM failed. PAM chloride, a salt of chlorine instead of iodine and having a greater solubility, was found to be quite equal to PAM both in effectiveness and toxicity, PAD was ineffective against parathion poisoning. Conclusion: TMB-4 may be a powerful remedy to rescue very severe cases of parathion poisoning, but because of its higher toxicity clinical dose should be determined carefully after many clinical tests.

収録刊行物

  • 産業医学

    産業医学 2 (10), 814-829, 1960

    社団法人 日本産業衛生学会

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