Effect of amitraz and chlordimeform on heart rate and pupil diameter in rats: mediated by alpha 2-adrenoreceptors.

Pupillary and cardiac responses to the insecticide/acaricide amitraz (0.03 to 1.0 mg/kg, iv) and chlordimeform (0.03 to 10.0 mg/kg, iv), as well as the alpha 2-adrenergic agonists clonidine (1 to 30 micrograms/kg, iv) and xylazine (10 to 300 micrograms/kg, iv), were investigated in rats anesthetized with an ether and pentobarbital combination. Amitraz, clonidine, and xylazine caused a dose-dependent mydriasis and bradycardia. The order of potency of the mydriatic and bradycardic effects was: clonidine greater than xylazine greater than amitraz. Chlordimeform did not cause mydriasis or bradycardia at the dosages studied. Amitraz-induced mydriasis and bradycardia were blocked by antagonists with alpha 2-adrenoreceptor blocking activity: yohimbine and phentolamine (2.5 mg/kg each, iv). In contrast, these effects of amitraz were not affected by prazosin (2.5 mg/kg, iv), an alpha 1-adrenoreceptor antagonist. In rats pretreated with reserpine (7.5 mg/kg, sc, 20 hr) and alpha-methyl-p-tyrosine (250 mg/kg, ip, 5 hr) to deplete catecholamine, amitraz (0.03-1.0 mg/kg, iv) produced mydriasis of similar magnitude as in the control animals. However, amitraz did not lower the heart rate in the pretreated animals as it did in the control animals. The results demonstrated that amitraz, a formamidine, induced mydriasis and bradycardia which were not observed with administration of another formamidine, chlordimeform. The data also suggest that amitraz-induced mydriasis is mediated by postsynaptic alpha 2-adrenoreceptors while amitraz-induced bradycardia is mediated by presynaptic alpha 2-adrenoreceptors.