EFFECTS OF ATROPINE-OXIME THERAPY ON CHOLINESTERASE ACTIVITY AND SURVIVAL OF ANIMALS POISONED WITH O,O-DIETHYL-O-(2-ISOPROPYL-6-METHYL-4-PYRIMIDINYL) PHOSPHOROTHIOATE

Brain and diaphragm cholinesterase (ChE) activity in rats was reduced to 22.6 ± 4.3 and 15.5 ± 6.3% (P = 0.95) of normal respectively 24 hours after oral dosage with 235 mg/kg (0.8 LD50) of O,O-diethyl-O-(2-isopropyl-6-methyl-4-pyrimidinyl) phosphorothioate (Diazinon). The ChE activity of brain and diaphragm in poisoned rats recovered gradually to 44.8 ± 8.9 and 62.6 ± 7.5% (P = 0.95) of normal, respectively 140 hours after poisoning. Treatment with 16 mg/kg of atropine im 10 minutes after poisoning followed 24 hours later by 30 mg/kg of pyridine 2-aldoxime methochloride (2-PAM Cl) by either the oral or iv route resulted in significant reactivation of diaphragm ChE levels compared to poisoned controls. The oral single LD50 of Diazinon in rats treated with 16 mg/kg of atropine im along with 30 mg/kg of 2-PAM Cl orally or iv was elevated 3.1 and 1.7 times, respectively. Administration of 2-PAM Cl to Diazinon-poisoned rabbits resulted in reactivation of inhibited blood ChE activity concurrent with decrease in signs of poisoning. Within 2 hours the animals were again weak and ataxic, and blood ChE showed renewed inhibition. These observations suggest that effective therapy of Diazinon intoxication requires the maintenance of a level of oxime high enough to reactivate inhibited ChE during the time in which active inhibitor is formed or available. This may be more readily achieved when 2-PAM Cl is given orally following an initial iv dose in conjunction with atropine given im. © 1969.