FLUOXETINE, A SELECTIVE SEROTONIN-UPTAKE INHIBITOR, ENHANCES THE ANTICONVULSANT EFFECTS OF PHENYTOIN, CARBAMAZEPINE, AND AMELTOLIDE (LY201116)

Dose-response curves for the prototypical anticonvulsants phenytoin (PHT) and carbamazepine (CBZ), and a novel anticonvulsant, ameltolide (LY201116), were determined with and without pretreatment with the selective serotonin-uptake inhibitor fluoxetine by maximal electroshock seizure (MES) test in mice. Fluoxetine (2.5, 5, and 10 mg/kg intraperitoneally, i.p.) produced a dose-related decrease in the ED50 values for the anticonvulsants (i.p. administration) to protect against MES-induced tonic-extensor seizures. Fluoxetine (10 mg/kg i.p.) also decreased the intravenous (i.v.) ED50 doses of the three anticonvulsants by a factor of approximately 2. These data suggest that fluoxetine, through its selective inhibition of serotonergic reuptake, may have beneficial advantages as compared with common antidepressant drugs in treatment of depressed patients with epilepsy and may also enhance the seizure control of prototypical anticonvulsants in treatment of epilepsy.