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Journal of Pharmacology And Experimental Therapeutics, Vol. 121, Issue 1, 96-106, 1957
Copyright © 1957 by American Society for Pharmacology and Experimental Therapeutics

MARKED POTENTIATION IN MAMMALIAN TOXICITY FROM SIMULTANEOUS ADMINISTRATION OF TWOANTICHOLINESTERASE COMPOUNDS

John P. Frawley 1, Henry N. Fuyat 1, Ernest C. Hagan 1, Jane R. Blake 1, and O. Garth Fitzhugh 1

1 Division of Pharmacology, Bureau of Biological and Physical Sciences, Food and Drug Administration, Department of Health, Education, and Welfare, Washington 25, D. C.

Data are presented to show up to 50-fold potentiation in the acute toxicity of EPN and malathion if they are administered simultaneously to dogs. The potentiation is marked but less for the rat. The potentiation from acute doses to dogs is associated with a marked increase in erythrocyte cholinesterase inhibition. Subacute experiments reveal that feeding of diets containing both EPN and malathion to dogs produces minimum blood cholinesterase inhibition at levels frac12 to [unknown] the level required for the individual compounds for similar effect. Subacute studies with rats reveal increased cholinesterase inhibition, but again to a lesser degree than with the dog.

Submitted on April 11, 1957




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Copyright © 1957 by the American Society for Pharmacology and Experimental Therapeutics.