オキシム剤PAMの新生化学的定量法並びに家兎の体内分布の消長について
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概要
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PAM (pyridine-2-aldoxime methiodide) is well approved as the most effective antidote against organophosphate poisoning, but as for its distribution in the blood excretion researches are very scarce owing to the lack of proper assay methods. A) On the determination of PAM The author invesigated a method using the qualitative color reaction of oximes in Feigl's "Spot Test", but found it unreliable because of the incomplete hydrolysis of PAM and the presence of inhibitory substances in biological samples. The biochemical method based on the reactivating effect of PAM on cholinesterase (ChE) which had been inhibited in advance by organophosphate in vitro was found quite satisfactory, and the following procedure was devised. 1. Biological materials are heated at 100℃ for one min. to separate protein and ChE contained in samples per se. 2. Human erythrocytes are used as ChE, which has been inhibited to the extent of 80-90% by Paraoxon, Dipterex or equivalent agent. 3. The ChE activity is measured by Hesterin-Miyazaki's colorimetric method. 4. PAM in samples is estimated by the reactivation rate of ChE, the assay range being 1.1-32γ/ml. B) On the distribution of PAM in rabbits Rabbits were given 80mg/kg of PAM intravenously or srbcutaneously and the amounts in the tissue were determined by the above method. 1. Levels in the brain and the spinal cord were low showing 5-6γ/g after 30 min., which were about one-sixth of those in other organs. The level after 2 hrs. was a little higher in animals by subcutanous route than those by intravenous route. 2. The highest content among all tissues was found in kidneys at 30 min. after the administration. The values decreased rapidly thereafter. This might suggest the prompt excretion of PAM in the urine. 3. Diaphragm contained higher amounts of PAM than other muscles. 4. In Heart, lung and blood the amount of PAM showed a prompt increase and a rapid decrease. From these results it may be concluded that, in emergencies the intravenous administration will be indicated to in sure higher levels of PAM quickly, while for the purpose to maintain its level in the organ thereafter the subcutaneous adminstration should be preferred. In moderate or mild cases, subcutaneous administration will always be indicated.
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