Ethyl beta-carboline carboxylate lowers seizure threshold and antagonizes flurazepam-induced sedation in rats.
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 act. Recently, ethyl beta-carboline-3-carboxylate (beta-CCE) has been identified in both human urine and rat brain. beta-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 receptor. Clinically and in animal studies, benzodiazepines have anti-convulsant, hypnotic and anxiolytic actions. We have therefore investigated whether beta-CCE exhibits any of these properties in rats. We report here that, in contrast to the benzodiazepines, beta-CCE lowers seizure threshold and reverses the sedative effect of flurazepam. If beta-CCE has a close structural relationship to the endogenous ligand, benzodiazepines may be antagonistic at the receptor site.
D000818:Animals; D001640:Bicuculline; D002243:Carbolines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005479:Flurazepam / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000494:pharmacology*; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects*; D011963:Receptors, GABA-A; D012640:Seizures / Q000139:chemically induced*
D002243:Carbolines; D007211:Indoles; D011955:Receptors, Drug; D011963:Receptors, GABA-A; C024915:beta-carboline-3-carboxylic acid ethyl ester; D005479:Flurazepam; D001640:Bicuculline