Benzodiazepine receptors studied in living primates by positron emission tomography: inverse agonist interactions.
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.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005442:Flumazenil / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010215:Papio; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D002243:Carbolines; D003292:Convulsants; D011963:Receptors, GABA-A; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D005442:Flumazenil; C036150:beta-carboline-3-carboxylic acid methyl ester