Studies on the Mechanism of Action of the Enhanced Protective Effect of Multiple versus a Single Dose of HI-6 against Soman Poisoning

摘要

Atropine pretreated rats given soman (650 micrograms/kg) survived an average 3.2 min. HI-6 (125 mg/kg, i.p.) increased survival time of all animals usually 3 - 6 h while multiple doses of HI-6 given post soman completely protected rats for at least 14 days. Soman treated animals given one dose of HI-6 developed short-lasting convulsions, followed by a convulsion free period then in about 1 1/2 h by a gradual return of severe tremors. A second dose of HI-6, unlike diazepam, quickly abolished the tremors. Diaphragm AChE activity was higher than control values following 1 dose of HI-6 1/2 h post soman but not at subsequent time intervals, while diaphragms from animals treated with HI-6 several times were higher than controls for at least 3 h. AChE activity remained virtually unchanged in all brain areas examined following either regimen. Skeletal muscles removed from animals which had developed delayed tremors had virtually no AChE activity nor did muscles from animals given a second dose of HI-6 which stopped the tremors. The results indicate that multiple HI-6 doses afford much better protection from soman than one dose. This enhanced protection may be due partially to the maintenance of AChE activity in the diaphragm for long periods and additionally to a direct effect on skeletal muscle resulting in improved respiratory function. These results indicate that HI-6 may be even more useful against soman poisoning than previously recognized if the dose schedule is altered.