ANTAGONISM OF ISONIAZID-INDUCED CONVULSIONS BY ABECARNIL IN MICE TOLERANT TO DIAZEPAM

The ability of the benzodiazepine receptor full agonist diazepam, the selective agonist abecarnil, and the partial agonist imidazenil to ant agonize convulsions induced by isoniazid (200 mg/kg, SC) was studied i n mice chronically treated with diazepam (3 mg/kg, IF, three times dai ly) or abecarnil (0.1 or 1 mg/kg, IF, three times daily or 6 mg/kg, SC , daily). Diazepam induced tolerance to its own anticonvulsant effect. In contrast, chronic treatment with abecarnil failed to induce tolera nce to its own anticonvulsant activity. Animals treated with abecarnil at 0.1 mg/kg developed cross-tolerance to imidazenil, whereas those t reated with 1 mg/kg became less sensitive to diazepam. Mice chronicall y treated with abecarnil at 6 mg/kg showed almost complete tolerance t o diazepam. Abecarnil was able to antagonize the convulsions elicited by isoniazid in diazepam-tolerant mice. These data indicate that chron ic administration of abecarnil, unlike that of classical benzodiazepin es, does not induce tolerance to its anticonvulsant effect, and that a becarnil overcomes tolerance induced by long-term treatment with the f ull agonist diazepam.