FAILURE OF FLUMAZENIL TO PRECIPITATE A WITHDRAWAL SYNDROME IN CATS CHRONICALLY TREATED WITH THE NEW ANXIOSELECTIVE BETA-CARBOLINE DERIVATIVE ABECARNIL

The effect of chronic administration of the novel anxiolytic beta-carb oline derivative, abecarnil oxy-4-methoxymethyl-beta-carboline-3-carbo xylate), was examined and compared with the capability of diazepam to induce physical dependence in cats. The acute administration of the be nzodiazepine receptor antagonist, flumazenil (20 mg/kg i.p.), to cats treated for 2 weeks with diazepam (7 mg/kg i.p., three times daily), i nduced a severe withdrawal syndrome characterized by the appearance of severe physical signs. Within minutes all cats displayed tremors, inc reased muscle tone, fear response, repeated vocalization and salivatio n. On the contrary, in all cats treated chronically (2 weeks) with abe carnil (7 mg/kg i.p. three times daily) the challenge dose of flumazen il failed to precipitate a clear abstinence syndrome. In fact, a pupil lary dilatation and a mild fear response were the only signs present 1 5-30 min after flumazenil administration. This finding indicates that abecarnil, a new potential therapeutic agent for anxiety disorders and seizures, might have advantages over classical benzodiazepines with r egard to development of physical dependence.