TOPIRAMATE IS A SULFAMATE-SUBSTITUTED MONOSACCHARIDE THAT IS INTENDED FOR USE AS AN ANTIEPILEPTIC DRUG. THE PRECISE MECHANISM BY WHICH TOPIRAMATE EXERTS ITS ANTISEIZURE EFFECT IS UNKNOWN; HOWEVER, ELECTROPHYSIOLOGICAL AND BIOCHEMICAL STUDIES OF THE EFFECTS OF TOPIRAMATE ON CULTURED NEURONS HAVE REVEALED THREE PROPERTIES THAT MAY CONTRIBUTE TO TOPIRAMATE'S ANTIEPILEPTIC EFFICACY. FIRST, ACTION POTENTIALS ELICITED REPETITIVELY BY A SUSTAINED DEPOLARIZATION OF THE NEURONS ARE BLOCKED BY TOPIRAMATE IN A TIME-DEPENDENT MANNER, SUGGESTIVE OF A STATE-DEPENDENT SODIUM CHANNEL BLOCKING ACTION. SECOND, TOPIRAMATE INCREASES THE FREQUENCY AT WHICH (GAMMA)-AMINOBUTYRATE (GABA) ACTIVATES GABA A RECEPTORS, AND ENHANCES THE ABILITY OF GABA TO INDUCE A FLUX OF CHLORIDE IONS INTO NEURONS, SUGGESTING THAT TOPIRAMATE POTENTIATES THE ACTIVITY OF THIS INHIBITORY NEUROTRANSMITTER. THIS EFFECT WAS NOT BLOCKED BY FLUMAZENIL, A BENZODIAZEPINE ANTAGONIST, NOR DID TOPIRAMATE INCREASE THE DURATION OF THE CHANNEL OPEN TIME, DIFFERENTIATING TOPIRAMATE FROM BARBITURATES THAT MODULATE GABA A RECEPTORS. THIRD, TOPIRAMATE ANTAGONIZES THE ABILITY OF KAINATE TO ACTIVATE THE KAINATE/AMPA ((ALPHA)-AMINO-3-HYDROXY-5-METHYLISOXAZOLE-4-PROPIONIC ACID; NON-NMDA) SUBTYPE OF EXCITATORY AMINO ACID (GLUTAMATE) RECEPTOR, BUT HAS NO APPARENT EFFECT ON THE ACTIVITY OF N-METHYL-D-ASPARTATE (NMDA) AT THE NMDA RECEPTOR SUBTYPE.