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.
Yakoub
L K
LK
Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Iraq.
Mohammad
F K
FK
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators; D003976:Diazinon / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007093:Imidazoles / Q000494:pharmacology*; D007306:Insecticides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D020926:Medetomidine; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control; D010276:Parasympatholytics / Q000494:pharmacology; D015996:Survival Rate
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D007093:Imidazoles; D007306:Insecticides; D010276:Parasympatholytics; C050701:atipamezole; D001285:Atropine; D020926:Medetomidine; D003976:Diazinon