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Levetiracetam inhibits glutamate transmission through presynaptic P/Q-type calcium channels on the granule cells of the dentate gyrus.
Br J Pharmacol 2009; 158(7):1753-62BJ

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.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19888964

Citation

Lee, Chun-Yao, et al. "Levetiracetam Inhibits Glutamate Transmission Through Presynaptic P/Q-type Calcium Channels On the Granule Cells of the Dentate Gyrus." British Journal of Pharmacology, vol. 158, no. 7, 2009, pp. 1753-62.
Lee CY, Chen CC, Liou HH. Levetiracetam inhibits glutamate transmission through presynaptic P/Q-type calcium channels on the granule cells of the dentate gyrus. Br J Pharmacol. 2009;158(7):1753-62.
Lee, C. Y., Chen, C. C., & Liou, H. H. (2009). Levetiracetam inhibits glutamate transmission through presynaptic P/Q-type calcium channels on the granule cells of the dentate gyrus. British Journal of Pharmacology, 158(7), pp. 1753-62. doi:10.1111/j.1476-5381.2009.00463.x.
Lee CY, Chen CC, Liou HH. Levetiracetam Inhibits Glutamate Transmission Through Presynaptic P/Q-type Calcium Channels On the Granule Cells of the Dentate Gyrus. Br J Pharmacol. 2009;158(7):1753-62. PubMed PMID: 19888964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Levetiracetam inhibits glutamate transmission through presynaptic P/Q-type calcium channels on the granule cells of the dentate gyrus. AU - Lee,Chun-Yao, AU - Chen,Chih-Chuan, AU - Liou,Horng-Huei, PY - 2009/11/6/entrez PY - 2009/11/6/pubmed PY - 2010/3/12/medline SP - 1753 EP - 62 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 158 IS - 7 N2 - 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/19888964/Levetiracetam_inhibits_glutamate_transmission_through_presynaptic_P/Q_type_calcium_channels_on_the_granule_cells_of_the_dentate_gyrus_ L2 - https://doi.org/10.1111/j.1476-5381.2009.00463.x DB - PRIME DP - Unbound Medicine ER -