Ethyl β-carboline carboxylate lowers seizure threshold and antagonizes flurazepam-induced sedation in rats

Publisher Website
Google Scholar
Abstract
The mammalian central nervous system possesses specific high-affinity binding sites for the benzodiazepines and considerable evidence suggests that these binding sites are the pharmacological receptors through which these compounds act1–6. Recently7, ethyl-β-carboline-3-carboxylate (β-CCE) has been identified in both human urine and rat brain. β-CCE may be closely related to the endogenous ligand for the benzodiazepine receptor—it shows an affinity for the receptor of the same order as that of clonazepam, one of the most potent benzodiazepines, and is the first non-diazepinoid structure to be identified with an affinity in the nanomolar range. Furthermore, it is selective for the benzodiazepine receptor7. Clinically and in animal studies, benzodiazepines have anti-convulsant, hypnotic and anxiolytic actions8. We have therefore investigated whether β-CCE exhibits any of these properties in rats. We report here that, in contrast to the benzodiazepines, β-CCE lowers seizure threshold and reverses the sedative effect of flurazepam. If β-CCE has a close structural relationship to the endogenous ligand, benzodiazepines may be antagonistic at the receptor site.