Further studies on the ethanol antagonism exhibited by 2(2-chloro-5-trifluoromethyl phenylimino) imidazolidine (St 587).
A lipid soluble alpha 1-adrenoceptor agonist 2-(2-chloro-5-trifluoromethyl phenylimino) imidazolidine (St 587) dose-dependently antagonized the hypnotic, hypothermic and respiratory depressant effects of ethanol in C57B1/6 mice. This effect was present whether St 587 was given before or after ethanol. St 587 did not block the pentobarbitone-induced hypnosis. It also did not influence the elimination of ethanol. Combined treatment with a subhypnotic dose of ethanol and St 587 resulted in marked hyperactivity in mice. This effect was completely abolished by pimozide pretreatment. It was inferred that the dopamine released from brain areas by this dose of ethanol together with the norepinephrine receptor activation offered by St 587 resulted in this hyperactivity. Cirazoline, a more potent alpha 1-adrenoceptor agonist than St 587 was relatively more effective than the latter in blocking the ethanol-induced hypnosis in mice. It seems that alpha 1-adrenoceptor stimulation is a major contributing factor to the ethanol antagonism exerted by St 587. This drug might prove to be useful in the treatment of acute ethanol intoxication and in understanding the mode of action of ethanol.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
C030655:St 587; D010868:Pimozide; D000431:Ethanol; D010424:Pentobarbital; D003000:Clonidine