Effects of zonisamide on K+ and Ca2+ evoked release of monoamine as well as K+ evoked intracellular Ca2+ mobilization in rat hippocampus

To clarify the effects of zonisamide (ZNS) on neurotransmission and intracellular Ca2+ mobilization, both Ca2+ and K+ evoked hippocampal releases of dopamine (DA) and serotonin (5-HT) were determined by in vivo microdialysis, and K+ (25 and 50 mM) evoked elevation of intracellular Ca2+ level was determined by fluorescence microscopy in vitro. Therapeutic concentrations of ZNS had different effects on Ca2+ and K+ evoked release of monoamine. ZNS stimulated Ca2+ evoked monoamine release, while ZNS inhibited K+ evoked monoamine release. ZNS inhibited K+ evoked elevation of hippocampal intracellular Ca2+ levels in a concentration dependent manner. These results suggest that ZNS inhibits the depolarization induced by neuronal excitation, whereas ZNS might enhance the N-type Ca2+ channel activity or N-type Ca2+ channel related exocytosis mechanisms. (C) 1999 Elsevier Science B.V. All rights reserved.