Insecticidal properties,antiesterase activities,and metabolism of methamidophos

Methamidophos is highly toxic to insects but at best is a moderate cholinesterase inhibitor. Evaluation of the kinetics of its housefly cholinesterase inhibition showed that its affinity for the enzyme and its phosphorylation and bimolecular inhibition rates are all relatively low. In vivo metabolism studies in houseflies provided evidence that it is not activated to a more effective cholinesterase inhibitor and indirect evidence also was obtained for its slow degradation. In vitro metabolism studies in housefly and mouse tissues provided additional evidence for its lack of activation and slow metabolic degradation. Compared to other effective organophosphorus insecticides, methamidophos was slow in producing acute symptoms of poisoning and cholinesterase inhibition and required the accumulation of comparatively high internal levels for toxic effects. However, in vivo cholinesterase inhibition studies provided evidence for the interrelationships of cholinesterase inhibition and toxic effects. Thus, its relative stability and low in vivo degradation appeared to be of critical importance in accumulating and maintaining a sufficient internal concentration for a sufficiently long period of time to permit the development of its slowly expressed toxicity.