Article date: December 2009
By: Chun‐Yao Lee, Chih‐Chuan Chen, Horng‐Huei Liou in Volume 158, Issue 7, pages 1753-1762
Background and purpose: Levetiracetam is an effective anti‐epileptic drug in the treatment of partial and generalized seizure. The purpose of the present study was to investigate whether levetiracetam regulates AMPA and NMDA receptor‐mediated excitatory synaptic transmission and to determine its site of action in the dentate gyrus (DG), the area of the hippocampus that regulates seizure activities.
Experimental approach: Whole‐cell patch‐clamp method was used to record the AMPA and NMDA receptor‐mediated excitatory postsynaptic currents (EPSCAMPA and EPSCNMDA) in the presence of specific antagonists, from the granule cells in the DG in brain slice preparations from young Wistar rats (60–120 g).
Key results: Levetiracetam (100 µM) inhibited both evoked EPSCAMPA and EPSCNMDA to an equal extent (80%), altered the paired‐pulse ratio (from 1.39 to 1.25), decreased the frequency of asynchronous EPSC and prolonged the inter‐event interval of miniature EPSCAMPA (from 2.7 to 4.6 s) without changing the amplitude, suggesting a presynaptic action of levetiracetam. The inhibitory effect of levetiracetam on evoked EPSCAMPA was blocked by ω‐agatoxin TK (100 nM), a selective P/Q‐type voltage‐dependent calcium channel blocker, but not by nimodipine (10 µM) or ω‐conotoxin (400 nM).
Conclusions and implications: These results suggest that levetiracetam modulated the presynaptic P/Q‐type voltage‐dependent calcium channel to reduce glutamate release and inhibited the amplitude of EPSC in DG. This effect is most likely to contribute to the anti‐epileptic action of levetiracetam in patients.
DOI: 10.1111/j.1476-5381.2009.00463.x
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