Role of carboxylesterases in the prevention and potentiation of N-methylcarbamate toxicity.
Pretreatment of rats with iso-OMPA one hour prior to each of the N-methylcarbamate insecticides, carbofuran, propoxur, or aldicarb, potentiated the toxicity of these carbamates threefold. None of these compounds alone in the dosage used produced toxic signs; however, carboxylesterase (CarbE) activity in a variety of organs including brain, muscle, liver, and plasma was significantly reduced, while acetylcholinesterase (AChE) activity was unchanged. Significant inhibition of AChE was observed after the combination of tetraisopropylpyrophosphoramide (iso-OMPA) with each one of these N-methylcarbamates. It is suggested that CarbEs are more sensitive than AChE to these N-methylcarbamates and inhibition of CarbE by iso-OMPA raises the concentration of N-methylcarbamates available to inhibit AChE resulting in increased toxicity. Other N-methylcarbamates such as physostigmine do not inhibit CarbE, nor are their toxicities potentiated by iso-OMPA.
Gupta
R C
RC
Breathitt Veterinary Center, Murray State University, Hopkinsville, KY.
Dettbarn
W D
WD
D000818:Animals; D002219:Carbamates / Q000633:toxicity*; D002235:Carbofuran / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000502:physiology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D007306:Insecticides / Q000633:toxicity*; D051381:Rats; D013770:Tetraisopropylpyrophosphamide / Q000494:pharmacology*
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D013770:Tetraisopropylpyrophosphamide; C020401:N-methylcarbamate; D002265:Carboxylic Ester Hydrolases; D002235:Carbofuran