Biochemical Mechanisms of Organophosphate Tolerance.
Annual summary rept. 1 Jul 84-31 Jul 85,
CONNECTICUT UNIV STORRS SCHOOL OF PHARMACY
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The lethality of organophosphate cholinesterase inhibitors is thought to result from depression of the respiratory center in the brain stem, constriction of and increased secretion by the airways, and paralysis of the respiratory musculature. While tolerance to the cholinergic toxicity of organophosphates has been well documented, such studies have not included investigations of the brain stem and extrapulmonary airways. Tolerance in mice to the insecticide malathion and in rats to Diisopropyfluorophosphate DFP is demonstrated. Male rats were injected, so with DFP over 14 days. Diminished signs of toxicity and return to normal weight gain indicated tolerance. The lesser amount of CHE inhibition in select brain regions may be mechanistically involved in OP tolerance.