Levetiracetam inhibits glutamate transmission through presynaptic P/Q‐type calcium channels on the granule cells of the dentate gyrus

摘要: Background and purpose:  Levetiracetam is an effective anti-epileptic drug in the treatment of partial generalized seizure. The purpose present study was to investigate whether levetiracetam regulates AMPA NMDA receptor-mediated excitatory synaptic transmission determine its site action dentate gyrus (DG), area hippocampus that seizure activities. Experimental approach:  Whole-cell patch-clamp method used record postsynaptic currents (EPSCAMPA EPSCNMDA) presence specific antagonists, from granule cells DG brain slice preparations young Wistar rats (60–120 g). Key results:  (100 µM) inhibited both evoked EPSCAMPA EPSCNMDA equal extent (80%), altered paired-pulse ratio (from 1.39 1.25), decreased frequency asynchronous EPSC prolonged inter-event interval miniature 2.7 4.6 s) without changing amplitude, suggesting a presynaptic levetiracetam. inhibitory effect on blocked by ω-agatoxin TK (100 nM), selective P/Q-type voltage-dependent calcium channel blocker, but not nimodipine (10 µM) or ω-conotoxin (400 nM). Conclusions implications:  These results suggest modulated reduce glutamate release amplitude DG. This most likely contribute patients.