The protective effect of the alpha2-agonist
medetomidine against the organophosphorus
insecticide diazinon-induced toxicosis was examined in male mice. Oral dosing of
diazinon at 75 and 100 mg/kg produced signs of toxicosis in mice characteristic of
cholinergic over-stimulation, and the percentages of deaths were 90 and 100%, respectively. Subcutaneous (s.c.) injection of
medetomidine at 0.05, 0.1 and 0.3 mg/kg, 15 min before
diazinon (75 mg/kg, orally) significantly and dose-dependently decreased the incidence of toxic manifestations, delayed the onset of
tremors and death, and increased the 24 h survival rates to 70, 80 and 100%, respectively. Similarly
medetomidine pretreatments (0.1 and 0.3 mg/kg, s.c) significantly protected the mice from the toxicity of a high dose (100 mg/kg, orally) of
diazinon, and increased the 24 h survival rates to 38 and 50%, respectively. The alpha2-antagonist
atipamezole significantly abolished the protective effect of
medetomidine. When
atropine sulfate (6 mg/kg, s.c.) was combined with
medetomidine (0.3 mg/kg, s.c.) the degree of protection against
diazinon toxicosis was more than that produced by either
drug alone. The data suggest that
medetomidine protected mice against
diazinon-induced toxicosis, and a combination of
medetomidine and
atropine produced an even greater degree of protection.