Benzodiazepine receptors studied in living primates by positron emission tomography: inverse agonist interactions.

Abstract

The convulsant actions of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and of methyl beta-carboline-3-carboxylate (beta-CCM) were evaluated in the baboon (Papio papio). DMCM, 0.6-4 mg/kg, induced epileptic seizures with short latency. DMCM convulsive seizures could be blocked by i.v. administration of the benzodiazepine agonist diazepam (10 mg). Similarly, beta-CCM, 0.3-3 mg/kg i.v., provoked generalized seizures in the baboons. These seizures were also reversed by the administration of propyl beta-carboline-3-carboxylate (3 mg/kg) or of diazepam (5 mg/kg). Combining the results from Positron Emission Tomography and the EEG assessments, benzodiazepine receptor occupancy by beta-CCM and DMCM was directly correlated with their convulsant actions in the living baboon. beta-CCM exerted its convulsant action in the living baboon at 76 and 74% benzodiazepine receptor occupancy in, respectively, occipital and temporal cortices whereas DMCM displayed a similar convulsive activity when only 58 and 65% of these receptors in the above regions were occupied.

• Authors: P Hantraye, C Chavoix, B Guibert, H Fukuda, E Brouillet, R H Dodd, C Prenant, M Crouzel, R Naquet, M Mazière
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 138 Issue 2 Pg. 239-47 (Jun 19 1987) ISSN: 0014-2999 [Print] Netherlands
• PMID: 3040433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbolines
• Convulsants
• Receptors, GABA-A
• methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate
• Flumazenil
• beta-carboline-3-carboxylic acid methyl ester

Topics

• Animals
• Binding, Competitive (drug effects)
• Carbolines (pharmacology)
• Cerebral Cortex (drug effects, metabolism)
• Convulsants (pharmacology)
• Dose-Response Relationship, Drug
• Electroencephalography
• Flumazenil (metabolism, pharmacology)
• Male
• Papio
• Receptors, GABA-A (drug effects, metabolism)
• Tomography, Emission-Computed