A beta-carboline antagonizes benzodiazepine actions but does not precipitate the abstinence syndrome in cats.
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.
Ongini
E
E
Marzanatti
M
M
Bamonte
F
F
Monopoli
A
A
Guzzon
V
V
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001570:Benzodiazepinones / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D002415:Cats; D003975:Diazepam / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004569:Electroencephalography; D005442:Flumazenil; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000209:etiology
D001570:Benzodiazepinones; D002243:Carbolines; D007211:Indoles; D011963:Receptors, GABA-A; D005442:Flumazenil; C035874:FG 7142; D003975:Diazepam