THE ANTICONVULSANT EFFECT OF THE BROAD-SPECTRUM ANTICONVULSANT LORECLEZOLE MAY BE MEDIATED IN PART BY SEROTONIN IN RATS - A MICRODIALYSIS STUDY

Loreclezole is an experimental anticonvulsant drug. We found previousl y that several established anticonvulsants increase extracellular sero tonin as measured by microdialysis. We have concluded that the increas e in extracellular serotonin and the anticonvulsant effect produced by these anticonvulsant drugs are related in a cause and effect manner. To determine if anticonvulsant doses of loreclezole increase extracell ular serotonin, we determined anticonvulsant dose-response relationshi ps in genetically epilepsy-prone rats (GEPRs). Then, we administered E D(99) doses of loreclezole to GEPRs and determined the effect on extra cellular serotonin as measured by microdialysis in the striatum. We co nclude that loreclezole produces a dose-related anticonvulsant effect in GEPRs and that anticonvulsant doses of loreclezole increase extrace llular serotonin in these animals.