| Title | Levetiracetam inhibits glutamate transmission through presynaptic P/Q-type calcium channels on the granule cells of the dentate gyrus. | | Author(s) | Lee CY, Chen CC, Liou HH | | Institution | Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan. | | Source | Br J Pharmacol 2009 Nov 3. | | Abstract | 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 (EPSC(AMPA) and EPSC(NMDA)) 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 microM) inhibited both evoked EPSC(AMPA) and EPSC(NMDA) 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 EPSC(AMPA) (from 2.7 to 4.6 s) without changing the amplitude, suggesting a presynaptic action of levetiracetam. The inhibitory effect of levetiracetam on evoked EPSC(AMPA) was blocked by omega-agatoxin TK (100 nM), a selective P/Q-type voltage-dependent calcium channel blocker, but not by nimodipine (10 microM) or omega-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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19888964 |
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