2,3-DIHYDROXY-6-NITRO-7-SULFAMOYLBENZO(F)QUINOX ALIGN ENHANCES THE PROTECTIVE ACTIVITY OF COMMON ANTIEPILEPTIC DRUGS AGAINST MAXIMAL ELECTROSHOCK-INDUCED SEIZURES IN MICE

NBQX dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline), a novel and se lective AMPA antagonist, was tested to evaluate its influence upon ant iconvulsant activity of common antiepileptic drugs in mice. NBQX (10, 20,40 mg/kg, i.p.) had no influence upon the threshold for electroconv ulsions. NBQX (10 mg/kg) enhanced the activity of anticonvulsant drugs decreasing their ED50s against maximal electroshock from 321 to 190 m g/kg for valproate, from 19.5 to 14.5 mg/kg for carbamazepine, from 3 1.0 to 21.4 mg/kg for phenobarbital, from 17.8 to 9.5 mg/kg for diphen ylhydantoin and from 19.5 to 10.5 mg/kg for diazepam. In addition, NBQ X (10 mg/kg) failed to impair motor performance and long-term memory d etermined in the chimney test and passive avoidance task. The combinat ions of NBQX (10 mg/kg) and carbamazepine, diphenylhydantoin or phenob arbital resulted in no adverse effects. Diazepam (10.5 mg/kg) alone im paired the motor performance and long-term memory and so it did when c ombined with NBQX. Also retention of the passive avoidance task and mo tor performance were impaired by valproate alone or given together wit h NBQX. Finally, NBQX (10 mg/kg) did not affect the plasma level of an y antiepileptic drug. It is concluded that non-NMDA glutamate receptor blockade results in the considerable enhancement of the efficacy of c ommon antiepileptic drugs.