Medetomidine protection against diazinon-induced toxicosis in mice

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.