EFFECT OF 5-FLUOROINDOLE-2-CARBOXYLIC ACID (AN ANTAGONIST OF THE NMDARECEPTOR-ASSOCIATED GLYCINE SITE) ON THE ANTICONVULSIVE ACTIVITY OF CONVENTIONAL ANTIEPILEPTIC DRUGS

5-Fluoroindole-2-carboxylic acid, an antagonist of the glycine site wi thin the NMDA receptor complex, administered intraperitoneally in dose s of 150 and 200mg/kg, 120min before electroconvulsions, significantly raised the convulsive threshold from 6.8 to 7.9 and 8.3mA, respective ly. At lower doses, it did not influence the threshold. However, letha lity was observed 24h after administration of the threshold-elevating doses of this glycine site antagonist. 5-Fluoroindole-2-carboxylic aci d (100mg/kg), applied together with carbamazepine, valproate or phenob arbital, significantly reduced their ED50 values against maximal elect roshock - from 13.9 to 7.5 mg/kg, from 291 to 242 mg/kg, and from 18.6 to 11.1 mg/kg, respectively. At the dose of 50 mg/kg, it also potenti ated the protective activity of carbamazepine. However, 5-fluoroindole -2-carboxylic acid, up to 100mg/kg, did not affect the anticonvulsive activity of diphenylhydantoin. When applied at doses equal to their ED 50 values against maximal electroshock-induced convulsions, carbamazep ine (13.9mg/kg), phenobarbital (18.6 mg/kg) and valproate (291mg/kg) d id not affect the motor performance of mice in the chimney test. 5-Flu oroindole-2-carboxylic acid (100mg/ kg) produced a significant motor i mpairment, at 50 mg/kg it did not affect the motor performance. The co mbined treatment of 5-fluoroindole-2-carboxylic acid (100 mg/kg) with carbamazepine, phenobarbital or valproate, providing a 50% protection against maximal electroshock, resulted in motor impairment. Only the c ombination of 5-fluoroindole-2-carboxylic acid (50 mg/kg) with carbama zepine (8.6mg/kg) did not significantly influence this parameter. Almo st all of the antiepileptic drugs studied, when administered at doses equal to their ED50 values against maximal electroshock, did not influ ence retention in the passive avoidance task, which is a measure of lo ng-term memory. Only valproate (291mg/kg) worsened long-term memory. T he combined treatment of 5-fluoroindole-2-carboxylic acid (100mg/kg) w ith carbamazepine or phenobarbital, providing a 50% protection against maximal electroshock, did not affect the retention. The combination o f 5-fluoroindole-2-carboxylic acid (100 mg/kg) with valproate (242 mg/ kg) caused a significant impairment of long-term memory and mortality of 50% of animals 24h following the administration. The results sugges t that the blockade of the strychnine-insensitive glycine site may lea d to an enhancement of the protective activity of some conventional an tiepileptic drugs, which is associated with pronounced side-effects an d lethality in some cases.