Biomaterial Database

RO 15-1788 selectively reverses antagonism of pentylenetetrazol-induced discriminative stimuli by benzodiazepines but not by barbiturates. 1982

T Gherezghiher, and H Lal

The specificity of ethyl 8-fluro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo (1,5-a) (1,4) benzodiazepine-3-carboxylate (RO 15-1788) in reversing the effectiveness of diazepam and des-methylclobazam, but not of pentobarbital, in antagonizing discriminative stimuli produced by pentylenetetrazol is described. Male hooded rats were trained to discriminate pentylenetetrazol-induced interoceptive discriminative-stimuli (IDS) in a two-lever choice paradigm on an FR10 schedule of food reinforcement. These IDS pharmacologically model verbal report of anxiogenic activity in humans. Diazepam (1,4 benzodiazepine), des-methylclobazam (1,5 benzo-diazepine), and pentobarbital antagonized pentylenetetrazol-IDS. RO 15-1788 neither generalized to nor antagonized pentylenetetrazol-IDS. It also did not cause convulsions in pentylenetetrazol sensitized rats at doses up to 40 mg/kg. It did, however, antagonize the action of diazepam (10 mg/kg) as well as that of des-methylclobazam (160 mg/kg) but not that of pentobarbital. These data suggest that RO 15-1788 is not an anxiomimetic, anxiolytic or a convulsant drug, but it is a specific and effective antagonist of anxiolytic action of benzodiazepines.

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
D010433	Pentylenetetrazole	A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.	Leptazole,Pentamethylenetetrazole,Pentetrazole,Cardiazol,Corasol,Corazol,Corazole,Korazol,Korazole,Metrazol,Metrazole,Pentazol,Pentylenetetrazol
D003975	Diazepam	A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.	7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D005442	Flumazenil	A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.	Flumazepil,Anexate,Lanexat,Ro 15-1788,Romazicon,Ro 15 1788,Ro 151788
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
D000927	Anticonvulsants	Drugs used to prevent SEIZURES or reduce their severity.	Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D001463	Barbiturates	A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are GABA MODULATORS used as HYPNOTICS AND SEDATIVES, as ANESTHETICS, or as ANTICONVULSANTS.
D001569	Benzodiazepines	A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.	Benzodiazepine,Benzodiazepine Compounds
D001570	Benzodiazepinones