Potentiation Between Cholinesterase Inhibitors.

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Abstract
Organic phosphate insecticides EPN (ethyl-p-nitrophenyl thionophosphonate), malathion, chlorothion and phostex (mixture of bis-(dialkoxyphosphinothioyl) disulfides), in all possible paired combinations, showed potentiated toxicities when administered orally to mice. The latter three compounds were all partially inactivated by incubation with rat liver slices. EPN inhibited this inactivation producing in vitro potentiation of brain cholinesterase inhibition. Combination of malathion and chlorothion showed a similar potentiation. Malathion combined with OMPA (octamethyl pyrophosphoramide), parathion or physostigmine showed no potentiation in toxicity, nor did any paired combination of EPN, parathion and OMPA. Potentiation appears to be caused by the interference of one compound with the inactivation of the other by the liver.