A beta-carboline antagonizes benzodiazepine actions but does not precipitate the abstinence syndrome in cats

Abstract

The beta-carbolines, which are potent ligands for benzodiazepine receptors, antagonize the pharmacological actions of benzodiazepines. In the cat, the stable beta-carboline derivative methylamide-beta-carboline-3-carboxylate, FG 7142, and the specific benzodiazepine antagonist Ro 15-1788 reversed behavioral and electroencephalographic (EEG) changes produced by a single dose of diazepam. Surprisingly, the beta-carboline did not elicit signs of withdrawal when given after 22 days of a daily dose regimen of diazepam, while Ro 15-1788 precipitated an acute abstinence syndrome largely characterized by tremors, increased muscle tone, back arching, myoclonic jerks and pupil dilatation. Unlike Ro 15-1788, the beta-carboline produced effects of its own such as behavioral states of arousal and fearfulness. These findings indicate that the beta-carboline functionally interacts with benzodiazepine receptors in a manner unlike that seen with typical agonists and antagonists.