ELSEVIER Life Sciences, Vol. 63, No. 13, pp. 1075-1088. 1998 Copyright 0 1998 Elsevier Science Inc. Printed in the USA. All rights reserved 0024-3205/98 $19.00 + .OO PI1 SOO24-3205(98)00230-6 MINIREVIEW ELECTROPHYSIOLOGICAL EFFECTS OF FELBAMATE Renato Corradetti* and Anna Maria Pugliese Department of Preclinical and Clinical Pharmacology “Mario Aiazzi-Mancini”, Universita di Firenze, Viale G.B. Morgagni 65, 50134 Firenze, Italy (Received in final form July 10, 1998) Felbamate is a broad spectrum antiepileptic drug recently introduced into clinical practice for controlling seizures in patients affected by Lennox-Gastaut epilepsy, complex partial seizures or otherwise intractable epilepsies. However, the cellular mechanisms by which the drug exerts its anticonvulsant actions are not fully understood. The aim of the present article is to outline the possible mechanisms of action of felbamate as suggested by findings obtained with electrophysiological approaches. Key Words: felbamate, antiepileptic drug, epilepsy, strychnine-insensitive glycine receptor, NMDA receptor, glutamate receptors, GABA receptors, sodium channels, calcium channels, long-term potentiation Felbamate (2-phenyl-1,3-propanediol dicarbamate: FBM) is a derivative of the antianxiety agent meprobamate which possesses anticonvulsant and neuroprotective properties. It is a novel antiepileptic drug which exhibits a wide spectrum of anticonvulsant actions and has been shown to be effective against complex partial seizures in adults and Lennox-Gastaut syndrome in children (1). FBM has high bioavailability and a long half-life. The drug is well absorbed in the gastrointestinal tract, extensively metabolized by the liver, and 90% of the drug is eliminated in the urine. The highest dosage used in clinical studies is 3,600 mg/day. In controlled double-blind trials, high plasma levels of the drug are correlated (2) with several acute adverse effects reported by patients: headache, nausea, anorexia, somnolence, dizziness and vomiting (3). Rare but serious adverse events include aplastic anemia (4) and hepatic failure (5). In the rat brain, after intravenous injection, FBM rapidly penetrates the blood-brain barrier with uniform distribution throughout the brain (6;7). *Address correspondence to: Dr. Renato Corradetti, M.D., Department of Preclinical and Clinical Pharmacology “Mario Aiazzi-Mrmcini”, Universiti di Fiinze, Viale G.B. Morgagni 65, 50134 Firenze, Italy, Tel: ++39(55)4271-246, Fax: ++39(55)4271-280. e-mail: corradet@serverl.pharm.unifi.it