The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam

摘要: Here, we show that the synaptic vesicle protein SV2A is brain binding site of levetiracetam (LEV), a new antiepileptic drug with unique activity profile in animal models seizure and epilepsy. The LEV-binding enriched vesicles, photoaffinity labeling purified vesicles confirms it has an apparent molecular mass ≈90 kDa. Brain membranes from mice lacking do not bind tritiated LEV derivative, indicating necessary for binding. related compounds to expressed fibroblasts, sufficient No was observed isoforms SV2B SV2C. Furthermore, there high degree correlation between affinities series derivatives fibroblasts brain. Finally, strong affinity compound its ability protect against seizures audiogenic mouse model These experimental results suggest acts by modulating function SV2A, supporting previous indications possesses mechanism action distinct other drugs. Further, these indicate proteins involved exocytosis, SV2 particular, are promising targets development CNS therapies.