THE PRECISE MECHANISM(S) BY WHICH ZONISAMIDE EXERTS ITS ANTISEIZURE EFFECT IS UNKNOWN. IN VITRO PHARMACOLOGICAL STUDIES SUGGEST THAT ZONISAMIDE BLOCKS SODIUM CHANNELS AND REDUCES VOLTAGE-DEPENDENT, TRANSIENT INWARD CURRENTS (T-TYPE CA2+ CURRENTS), CONSEQUENTLY STABILIZING NEURONAL MEMBRANES AND SUPPRESSING NEURONAL HYPERSYNCHRONIZATION. IN VITRO BINDING STUDIES HAVE DEMONSTRATED THAT ZONISAMIDE BINDS TO THE GABA/BENZODIAZEPINE RECEPTOR IONOPHORE COMPLEX IN AN ALLOSTERIC FASHION WHICH DOES NOT PRODUCE CHANGES IN CHLORIDE FLUX. OTHER IN VITRO STUDIES HAVE DEMONSTRATED THAT ZONISAMIDE (10-30 ?G/ML) SUPPRESSES SYNAPTICALLY-DRIVEN ELECTRICAL ACTIVITY WITHOUT AFFECTING POSTSYNAPTIC GABA OR GLUTAMATE RESPONSES (CULTURED MOUSE SPINAL CORD NEURONS) OR NEURONAL OR GLIAL UPTAKE OF [3H]-GABA (RAT HIPPOCAMPAL SLICES). THUS, ZONISAMIDE DOES NOT APPEAR TO POTENTIATE THE SYNAPTIC ACTIVITY OF GABA. IN VIVO MICRODIALYSIS STUDIES DEMONSTRATED THAT ZONISAMIDE FACILITATES BOTH DOPAMINERGIC AND SEROTONERGIC NEUROTRANSMISSION. ZONISAMIDE ALSO HAS WEAK CARBONIC ANHYDRASE INHIBITING ACTIVITY, BUT THIS PHARMACOLOGIC EFFECT IS NOT THOUGHT TO BE A MAJOR CONTRIBUTING FACTOR IN THE ANTISEIZURE ACTIVITY OF ZONISAMIDE.