[Experimental studies on the efficacy of PAM against sumithion poisoning]

The efficacy of 2-Pyridine aldoximide methiodide (PAM) for lethal acute poisoning by fenitrothion (FNT) was investigated in mice and dogs. Sumithion (FNT 51.7%, emulsifiers 12.5% and xylol 35.8%) was used as fenitrothion. 1. FNT at 1500 mg/kg was administered orally to mice. After ten minutes 50 mg/kg of PAM was injected once iv, and plasma, erythrocyte, brain, liver and kidney ChE activities were investigated 30 and 60 min later. Recovery in ChE activity was found in every organ but the brain at 30 min, but no efficacy of PAM was observed at 60 min. 2. After administering 1500 mg/kg of FNT orally to mice, the life-saving effect was studied from the changes in mortality due to variation of PAM route, dosage and number of administrations. With oral administration of 1500 mg/kg of FNT, 75 to 85% of the animals died. The mortality ranged from 80 to 95% when the animals received a single intravenous injection of 50 mg/kg of PAM between zero and 60 min following the FNT administration. Thus, a single intravenous administration of PAM at 50 mg/kg showed no life-saving effect on the animals given FNT. However, the mortality was reduced to 45% when the animals received repeated subcutaneous injections of 20 mg/kg of PAM at a 3-hr interval from just after administration of FNT over 24-hr. In other repeated subcutaneous injection experiments, the mortality ranged from about 55 to 65%. In any PAM-treated group, the survival time was prolonged. This life-prolonging effect was more marked in the case of repeated subcutaneous injections of PAM by 12-hr and even more by 24-hr, than in the case of a single intravenous injection. FNT treatment caused marked salivation and watery diarrhea, and PAM clearly inhibited these signs of the muscarinic action of FNT. There was a high relationship between this inhibitory effect of PAM on the muscarinic action and its life-prolonging or life-saving effect. 3. PAM (150 mg/animal/shot, iv) was given 12 or 13 times during 7 hr from 10 min (4 animals), 3 hr (1 animal) and 6 hr (2 animals) after administration of FNT at 150 mg/kg. The effects of PAM on survival, plasma ChE activity, plasma protein (TP) and hematocrit (Ht) values were examined. The 3 dogs given FNT alone all died within 53 hr of administration, whereas 6 out of 7 animals treated with PAM survived.(ABSTRACT TRUNCATED AT 400 WORDS)