title: Failure of Ro 15-4513 to antagonize ethanol in rat lines selected for differential sensitivity to ethanol and in Wistar rats.
abstract: An imidazobenzodiazepine, Ro 15-4513, acting as a partial inverse agonist at the central benzodiazepine receptors has been recently reported to reverse efficiently the intoxicating effects of ethanol. In studies designed to delineate the role of benzodiazepine receptors in the ethanol-induced motor impairment difference between two rat lines selectively bred for high and low sensitivity to ethanol, however, we could not antagonize the effects of ethanol by Ro 15-4513 in the tilting plane and horizontal wire tests. Neither could we observe any consistent antagonism of ethanol actions in Han:Wistar rats, although we used a wide range of Ro 15-4513 doses, injected the drug intraperitoneally or intragastrically and before or after ethanol administration, and carried out the tests for motor impairment (rotarod, horizontal wire test and intoxication rating) at various times after the drug administration. The ex vivo assay of flunitrazepam binding in brain homogenates revealed the presence of compound(s) inhibiting the binding after administration of Ro 15-4513. Ro 15-4513 antagonized the motor impairing effects of lorazepam. In conclusion, Ro 15-4513 failed to function as a specific antagonist of moderate doses of ethanol in several tests for motor impairment in different rat lines.
authors.affiliation: Research Laboratories of the Finnish State Alcohol Company (Alko Ltd.), Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Hellevuo
authors.forename: E R
authors.initials: ER
authors.lastname: Korpi
mesh_terms: D000818:Animals; D001386:Azides / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism; D008140:Lorazepam / Q000037:antagonists & inhibitors; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013045:Species Specificity
chemical_list: D001386:Azides; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol; D005445:Flunitrazepam; C042957:Ro 15-4513; D008140:Lorazepam