Intravenous administration of 3-carboethoxy-β-carboline (β-CCE, 10 mg/kg) to rats resulted in multiple bursts of rhythmic waves (2-4 second duration, 5-7 Hz) with amplitudes of 100-250 μV. Pretreatment of animals with the benzodiazepine receptor antagonist CGS 8216 prevented the electroencephalographic seizures elicited by β-CCE. This dose of CGS 8216 did not produce any electroencephalographic abnormalities when administered alone. These observations suggest that the electroencephalographic seizures elicited by β-CCE are mediated via an interaction with benzodiazepine receptors. An in vitro study of the rate of degradation of β-CCE and 3-carbomethoxy-β-carboline (β-CCM) in rat plasma demonstrated that the rate of degradation of the former compound was three times more rapid than the latter. These observations, taken together with previous studies demonstrating that parenteral administration of β-CCM elicits tonic and clonic seizures, suggests that pharmacokinetic factors may be involved in defining the pharmacologic profile of β-carboline-3-carboxylic acid esters.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)