Amitraz-induced glucose intolerance in rats: antagonism by yohimbine but not by prazosin.

Amitraz (N'-[2,4-dimethylphenyl]-N-[(2,4-dimethylphenyl)imino]-N- methylmethanimidamide) is a formamidine insecticide/acaricide that increases plasma glucose and decreases plasma insulin concentrations in dogs when applied topically. Because amitraz activates alpha 2-adrenoceptors in numerous tissues, in this study we used rats as a model to determine whether these effects of amitraz are mediated by alpha 2-adrenoceptors. The i.v. injection of amitraz (0.1, 0.3, and 1 mg/kg) followed by i.v. glucose injection (1 g/kg) induced a dose-dependent glucose intolerance characterized by hypoinsulinemia. At 1 mg/kg, amitraz completely blocked the insulin release induced by i.v. glucose administration. The alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg, i.v.) prevented the effects of amitraz, but the alpha 1-adrenoceptor antagonist prazosin (0.3 mg/kg, i.v.) did not. The results suggested that one mechanism by which amitraz prolongs glucose-induced hyperglycemia is via inhibition of insulin release and this effect is mediated by alpha 2-adrenoceptors.