RO15-4513 but not FG-7142 reverses anticonvulsant effects of ethanol against bicuculline- and picrotoxin-induced convulsions in rats. 1989

S K Kulkarni, and M K Ticku
University of Texas Health Science Center, Department of Pharmacology, San Antonio 78284-7764.

The reversal of anticonvulsant effect of ethanol against chemoconvulsions by RO15-4513 was investigated in rats as this novel imidazobenzodiazepine (ethyl-8 azido-5, 6-dihydro-5-methyl-6-Oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate) is reported to antagonize the acute behavioral and biochemical effects of ethanol in animals. Reversal of ethanol effects on onset of myoclonic jerks, tonic extensor phase, mortality time and percent protection against mortality were compared with not only other anticonvulsant pentobarbital but also with another inverse agonist FG-7142. Pretreatment with RO15-4513 (4 mg/kg) reversed the protective effect of ethanol against bicuculline-induced tonic extensor phase and mortality (87%). This response was sensitive to reversal by RO15-1788 (10 mg/kg). However, onset of myoclonic jerks and duration of clonus were not significantly altered. It also reversed the effect against picrotoxin but the reversal against mortality was up to 50%. As compared to ethanol, RO15-4513 reversed partially the protective effect of pentobarbital against bicuculline- and picrotoxin-induced convulsions. FG-7142 failed to reverse the protective effect of ethanol and pentobarbital against bicuculline-induced tonic extensor phase although it reversed the effect against onset and mortality. It had no effect on the protective effect against picrotoxin-induced convulsions. Both RO15-4513 and FG-7142 possessed proconvulsant effects against bicuculline but not against picrotoxin. These observations suggest that RO15-4513 has a more preferential action against ethanol effects as compared to the other inverse agonist.

UI MeSH Term Description Entries
D008297 Male Males
D010424 Pentobarbital A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236) Mebubarbital,Mebumal,Diabutal,Etaminal,Ethaminal,Nembutal,Pentobarbital Sodium,Pentobarbital, Monosodium Salt,Pentobarbitone,Sagatal,Monosodium Salt Pentobarbital
D010852 Picrotoxin A mixture of PICROTOXININ and PICROTIN that is a noncompetitive antagonist at GABA-A receptors acting as a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates. 3,6-Methano-8H-1,5,7-trioxacyclopenta(ij)cycloprop(a)azulene-4,8(3H)-dione, hexahydro-2a-hydroxy-9-(1-hydroxy-1-methylethyl)-8b-methyl-, (1aR-(1aalpha,2abeta,3beta,6beta,6abeta,8aS*,8bbeta,9S*))-, compd. with (1aR-(1aalpha,2abeta,3beta,6beta,6abeta,8,Cocculin
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002243 Carbolines A group of pyrido-indole compounds. Included are any points of fusion of pyridine with the five-membered ring of indole and any derivatives of these compounds. These are similar to CARBAZOLES which are benzo-indoles. Carboline,Pyrido(4,3-b)Indole,Beta-Carbolines,Pyrido(4,3-b)Indoles,Beta Carbolines
D000345 Affinity Labels Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids. Affinity Labeling Reagents,Labeling Reagents, Affinity,Labels, Affinity,Reagents, Affinity Labeling
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001067 Appetite Depressants Agents that are used to suppress appetite. Anorectic,Anorectic Agent,Anorectics,Anorexic Drug,Anorexigenic Drug,Appetite Depressant,Appetite Suppressant,Appetite Suppressants,Appetite-Depressing Drug,Appetite-Suppressant Drug,Anorectic Agents,Anorexic Drugs,Anorexigenic Drugs,Appetite-Depressing Drugs,Appetite-Suppressant Drugs,Agent, Anorectic,Agents, Anorectic,Appetite Depressing Drug,Appetite Depressing Drugs,Appetite Suppressant Drug,Appetite Suppressant Drugs,Depressant, Appetite,Depressants, Appetite,Drug, Anorexic,Drug, Anorexigenic,Drug, Appetite-Depressing,Drug, Appetite-Suppressant,Drugs, Anorexic,Drugs, Anorexigenic,Drugs, Appetite-Depressing,Drugs, Appetite-Suppressant,Suppressant, Appetite,Suppressants, Appetite
D001386 Azides Organic or inorganic compounds that contain the -N3 group. Azide

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