Attenuation of ethanol intoxication by alpha-2 adrenoceptor antagonists.
The interaction of a highly potent and selective alpha-2 adrenoceptor antagonist, atipamezole with ethanol was investigated in tests assessing a number of ethanol's behavioral effects. Atipamezole antagonized ethanol's effects on directed exploration in a holeboard test, reduced observer-rated intoxication and also reduced the duration of loss of righting reflex caused by ethanol. Similar effects were produced by another alpha-2 adrenoceptor antagonist idazoxan. The magnitude of the effects was comparable to that produced in the same animal models by the imidazodiazepine Ro 15-4513, which antagonizes ethanol by an action at central benzodiazepine receptors. Whereas Ro 15-4513 possesses marked behavioral effects on its own, atipamezole is comparatively inactive in all paradigms so far tested. The data suggest that alpha-2 adrenoceptors can play an important role in modulating the intoxicating effects of ethanol.
Lister
R G
RG
Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892.
Durcan
M J
MJ
Nutt
D J
DJ
Linnoila
M
M
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000435:Alcoholic Intoxication / Q000378:metabolism*; D000818:Animals; D001386:Azides / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D000431:Ethanol / Q000037:antagonists & inhibitors*; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology*; D051379:Mice; D011963:Receptors, GABA-A / Q000378:metabolism; D012640:Seizures / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D001386:Azides; D004146:Dioxanes; D007093:Imidazoles; D011963:Receptors, GABA-A; C050701:atipamezole; D001569:Benzodiazepines; D000431:Ethanol; C042957:Ro 15-4513; D019329:Idazoxan