EFFECT OF THE BETA-CARBOLINE ABECARNIL ON SPINAL REFLEXES IN MICE ANDON MUSCLE TONE IN GENETICALLY SPASTIC RATS - A COMPARISON WITH DIAZEPAM

Abecarnil is a beta-carboline agonist at benzodiazepine receptors with potent anxiolytic activity but no muscle relaxant side effects in rod ents. Clinical experience suggests that changes in the muscle tone ind uced by benzodiazepines are related to their effects on spinal reflexe s. The authors therefore analyzed the effect of treatment with abecarn il on spinal monosynaptic (Hoffmann reflexes) and polysynaptic (flexor ) reflexes in mice and the influence of abecarnil on muscle tone in ge netically spastic rats. The i.v. administration of abecarnil in mice ( dose range, 0.02-1 mg/kg) depressed flexor reflexes in a dose-dependen t manner; Hoffmann reflexes remained unchanged. Administration of diaz epam i.v. (0.01-1 mg/kg) also reduced flexor reflexes and had little o r no effect on Hoffmann reflexes. In genetically spastic rats, i.v. ad ministration of abecarnil (10-30 mg/kg) decreased the muscle tone in a dose- and time-dependent manner. A similar muscle relaxant effect was observed in such rats after i.v. administration of diazepam (0.1-0.8 mg/kg). By contrast, i.p. administration of abecarnil in mice did not influence spinal reflexes up to the dose of 1 mg/kg and, in geneticall y spastic rats, did not affect muscle tone up to the dose of 100 mg/kg . Administration of diazepam i.p. (1 mg/kg) depressed flexor reflexes in mice and over the range 0.2 to 5 mg/kg produced a dose- and time-de pendent decrease of muscle tone in genetically spastic rats. The muscl e relaxant effect of i.p. diazepam could be antagonized by i.p. admini stered abecarnil. These studies thus demonstrate that i.v. but not i.p . administration of abecarnil may result in muscle relaxant action in mice and in genetically spastic rats.