Targeting SV2A for Discovery of Antiepileptic Drugs

Rafal M. Kaminski, Michel Gillard and Henrik Klitgaard

in Jasper's Basic Mechanisms of the Epilepsies

Fourth edition

Published on behalf of ©Jeffrey L. Noebels, Massimo Avoli, Michael A. Rogawski, Richard W. Olsen, and Antonio V. Delgado-Escueta

Published in print July 2012 | ISBN: 9780199746545
Published online April 2013 | e-ISBN: 9780199322817 | DOI:

Series: Contemporary Neurology Series

Targeting SV2A for Discovery of Antiepileptic Drugs

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Synaptic vesicle 2A constitutes the unique binding site for LEV and plays an important role in synaptic vesicle function. Affinity–potency correlations in several models of partial and generalized epilepsy indicate that SV2A is a broad-spectrum anticonvulsant target. The anticonvulsant activity of LEV is closely linked with occupancy and availability of SV2A, whereas SV2A deficiency leads to increased seizure vulnerability and accelerated epileptogenesis. Taken together, existing experimental data prove that SV2A plays a crucial role in mediating the anticonvulsant action of LEV in vivo and indicate that the SV2A protein represents an important and well-validated target for the discovery of novel AEDs. Finally, the finding that SV2A protein is a clinically validated target for epilepsy has triggered further discovery programs exploring the therapeutic potential for SV2A ligands with different binding properties.

Chapter.  5723 words.  Illustrated.

Subjects: Neurology

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