REACTIVATION BY PYRIDINIUM ALDOXIME METHOCHLORIDE (PAM) OF INHIBITED CHOLINESTERASE ACTIVITY IN DOGS AFTER POISONING WITH PINACOLYL METHYLPHOSPHONOFLUORIDATE (SOMAN)

¹ Physiology Department, Medical Research Laboratory, U.S. Army Edgewood Arsenal, Maryland

Pyridinium aldoxime methochloride (PAM) was used to study the causes underlying the previously reported failure to reactivate cholinesterase (ChE) inhibited by pinacolyl methylphosphonofluoridate (soman). By inhibition of erythrocyte ChE at 0°C and pH 8.8, conversion to a nonreactivatable state, "aging," was minimized. Equilibration of the preparation to 37°C and adjustment of the pH to 7.35 initiated rapid aging. The rates of aging of dog erythrocyte ChE inhibited by soman in vitro and in vivo were not significantly different, with half-times of 5.33 and 5.55 min, respectively. After inhibition with soman the rate of aging of dog erythrocyte ChE could be markedly diminished by the addition of PAM to 1.25 x 10^-3 M in vitro or by the injection of 104 mg/kg of PAM in vivo permitting reactivation of the inactivated ChE enzyme activity. Concurrent measurements of brain and diaphragm ChE activity in dogs poisoned with soman showed reactivation to occur only in the latter tissue. The close correlation between in vitro and in vivo rates of aging suggests that in a given species estimation of the rate of aging of red blood cell ChE after inhibition with an organophosphate in vitro would be useful as a guide to the time during which oxime therapy would be effective in vivo in case of intoxication by the same anticholinesterase.

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