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.

• Authors: E Ongini, M Marzanatti, F Bamonte, A Monopoli, V Guzzon
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 86 Issue 1-2 Pg. 132-6 ( 1985) ISSN: 0033-3158 [Print] Germany
• PMID: 2991962 (Publication Type: Journal Article)

Chemical References

• Benzodiazepinones
• Carbolines
• Indoles
• Receptors, GABA-A
• Flumazenil
• FG 7142
• Diazepam

Topics

• Animals
• Behavior, Animal (drug effects)
• Benzodiazepinones (pharmacology)
• Brain (drug effects)
• Carbolines (pharmacology)
• Cats
• Diazepam (adverse effects, antagonists & inhibitors)
• Electroencephalography
• Flumazenil
• Humans
• Indoles (pharmacology)
• Receptors, GABA-A (drug effects)
• Substance Withdrawal Syndrome (etiology)