Ethanol and benzodiazepines. The influence of CGS 8216 on the ethanol-induced hypothermia and motor incoordination in mice and rats.
Ethanol has pharmacological profile very similar to benzodiazepines which facilitate GABA-ergic neurotransmission. In addition, a lot of ethanol-induced effects are partially antagonized by Ro 15-4513, a benzodiazepine inverse agonist. In our study, the influence of CGS 8216, another benzodiazepine inverse agonist, on the hypothermic (3.5 g/kg in mice, 3.0 g/kg in rats) and disturbing the motor coordination (3.2 g/kg in mice, 2.5 g/kg in rats, aerial righting reflex) effects of ethanol was investigated. The hypothermic effects of ethanol were antagonized in mice, and significantly attenuated in rats by CGS 8216 (10 and 20 mg/kg). Ethanol-induced motor incoordination was significantly diminished by 10 and 20 mg/kg of CGS 8216 in mice but not in rats. These data suggest that some effects of ethanol may result from the intensification of benzodiazepine/GABA-ergic activity. In addition, they let us presume that the activity of CGS 8216 is connected with a benzodiazepine receptor named BZ-1 or omega 1. The results indicate the need of further work on the benzodiazepine inverse agonists for use in treatment of ethanol poisoning.
Fidecka
S
S
Department of Pharmacodynamics, Medical Academy, Lublin, Poland.
Langwínski
R
R
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D007036:Hypothermia, Induced; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects
D002492:Central Nervous System Depressants; D018755:GABA Agonists; D018756:GABA Antagonists; D011720:Pyrazoles; D001569:Benzodiazepines; D000431:Ethanol; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one