Benzodiazepine receptors studied in living primates by positron emission tomography: antagonist interactions

Abstract The convulsant actions of methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM) and of methyl β-carboline-3-carboxylate (β-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, βCCM, 0.3–3 mg/kg i.v., provoked generalized seizures in the baboons. These seizures were also reversed by the administration of propyl β-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 β-CCM and DMCM was directly correlated with their convulsant actions in the living baboon. β-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.