Bokonjic_1987_Arch.Int.Pharmacodyn.Ther_288_309

Protective and reactivating effects of oximes HI-6 and PAM-2, combined with atropine and diazepam, were investigated in quinalphos-poisoned rats. In protective experiments, atropine and diazepam decreased acute toxicity of the insecticide 3.3 times. Later administration of a single injection of oximes led to further improvement of protective indexes which were 1.45 (PAM-2) and 1.52 (HI-6) times larger. Plasma HI-6 concentrations below 1 microgram/ml, continuously maintained by osmotic minipumps and supported by a single administration of atropine and diazepam, protected animals from 18.6 LD50 of quinalphos, while its higher concentrations (ranging from 1 to 5.4 micrograms/ml) provided markedly better protection (up to 72 LD50). Corresponding plasma PAM-2 concentrations were even more effective in overcoming toxic effects of quinalphos. PAM-2 concentrations, continuously maintained in plasma, were distinctly better in protecting and reactivating peripheral cholinesterase activity than corresponding HI-6 concentrations in the case of quinalphos poisoning. On the basis of our findings we suggest that continuous maintenance of low oxime concentrations is preferred to single oxime administration in the therapy of organophosphate intoxications.