ro-5-3663 and methyl-6-7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate

Drugs which are agonists at benzodiazepine receptors produce many interesting behavioural effects, and amongst these are the stimulation of food, water and salt intake. This review examines the evidence for benzodiazepine effects on these forms of ingestion, and makes tentative proposals about their modes of action. The recent advent of putative benzodiazepine antagonists and inverse agonists provides important new pharmacological tools for the analysis of factors which control ingestion. Preliminary data on examples of such drugs are considered. Anorectic effects of inverse agonists are described. It is clear, though, that the categorization of a drug in one test situation may not apply to another. For example, the compound Ro15-1788 appears as a specific antagonist in one test, a partial agonist in another, and apparently lacks effect in a third. We are not yet sufficiently forward in our understanding of drug actions at benzodiazepine receptors, and their interactions with particular test circumstances, to predict and account for divergent effects of this kind.

Topics: Animals; Anti-Anxiety Agents; Appetite; Appetite Depressants; Benzodiazepines; Benzodiazepinones; Carbolines; Chlordiazepoxide; Chlorides; Choice Behavior; Diazepam; Drinking Behavior; Feeding Behavior; Flumazenil; Food Deprivation; Food Preferences; gamma-Aminobutyric Acid; Ion Channels; Midazolam; Picrotoxin; Punishment; Pyrazoles; Receptors, GABA-A; Satiation; Sodium Chloride; Species Specificity

1. The proconvulsant effects of the imidazodiazepine Ro 15-4513, were investigated in mice by use of intravenous infusion of a variety of convulsant drugs. 2. Dose-response and time course studies of Ro 15-4513 against gamma-aminobutyric acid (GABA) antagonists were performed. On the basis of these studies a maximally effective dose of 5 mg kg-1 was administered 5 min before the determination of seizure thresholds in subsequent experiments. 3. Ro 15-4513 (5 mg kg-1) significantly lowered seizure thresholds to pentylenetetrazole, bicuculline and the convulsant benzodiazepine Ro 5-3663, but failed to alter seizure thresholds to picrotoxin, strychnine, caffeine and quipazine. 4. Ro 15-4513 significantly raised seizure threshold to the benzodiazepine receptor inverse agonist methyl 6,7-dimethoxy-4 ethyl-beta-carboline-3-carboxylate (DMCM). 5. These results are discussed in relation to other studies investigating the proconvulsant and alcohol-antagonizing effects of Ro 15-4513.

Topics: Animals; Azides; Benzodiazepines; Benzodiazepinones; Bicuculline; Carbolines; Convulsants; Drug Interactions; Male; Mice; Pentylenetetrazole; Picrotoxin; Seizures