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Potentiation Between Cholinesterase Inhibitors.
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1958
Year
PharmacotherapyExperimental PharmacologyToxicological MechanismMolecular PharmacologyMedicinal ChemistryBorderline PotentiationToxicologyInsecticideInhibitory ActivityBiochemistryShowed PotentiationPharmacological AgentNeuropharmacologyExperimental ToxicologyPharmacologyNatural SciencesVitro PotentiationMedicineDrug Discovery
SummaryOrganic phosphate insecticides EPN, malathion, chlorothion and phostex, in all possible paired combinations administered simultaneously to mice showed potentiation in their oral toxicities. Some potentiation was observed even when EPN was given 24 hours before malathion. Malathion plus BFP showed borderline potentiation, whereas malathion combined with OMPA, parathion or physostigmine showed no potentiation, nor did EPN plus parathion, EPN plus OMPA or OMPA plus parathion. Malathion, chlorothion and phostex were partially inactivated by incubation with rat liver slices. EPN inhibited inactivation of malathion, chlorothion and phostex, producing an in vitro potentiation of cholinesterase inhibition. Potentiation in all cases found so far appears to be caused by interference by one compound with inactivation of the other by liver, or by a mutual interference with inactivation through a competition for a specific enzyme site.