A New SV2A Ligand for Epilepsy
نویسنده
چکیده
Since the 1970s, racetams have been in use as cognitive enhancers. Levetiracetam was discovered to have antiseizure activity in animal models and was then found to bind to SV2A in synaptic and endocrine vesicles. Brivaracetam, an analog of levetiracetam, was identified in a medicinal chemistry campaign with the objective of discovering analogs with higher affinity at racetam-binding sites and greater antiseizure potency.
منابع مشابه
Synaptic Vesicle Glycoprotein 2A Ligands in the Treatment of Epilepsy and Beyond
The synaptic vesicle glycoprotein SV2A belongs to the major facilitator superfamily (MFS) of transporters and is an integral constituent of synaptic vesicle membranes. SV2A has been demonstrated to be involved in vesicle trafficking and exocytosis, processes crucial for neurotransmission. The anti-seizure drug levetiracetam was the first ligand to target SV2A and displays a broad spectrum of an...
متن کاملThe synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam.
Here, we show that the synaptic vesicle protein SV2A is the brain binding site of levetiracetam (LEV), a new antiepileptic drug with a unique activity profile in animal models of seizure and epilepsy. The LEV-binding site is enriched in synaptic vesicles, and photoaffinity labeling of purified synaptic vesicles confirms that it has an apparent molecular mass of approximately 90 kDa. Brain membr...
متن کاملIdentification of the antiepileptic racetam binding site in the synaptic vesicle protein 2A by molecular dynamics and docking simulations
Synaptic vesicle protein 2A (SV2A) is an integral membrane protein necessary for the proper function of the central nervous system and is associated to the physiopathology of epilepsy. SV2A is the molecular target of the anti-epileptic drug levetiracetam and its racetam analogs. The racetam binding site in SV2A and the non-covalent interactions between racetams and SV2A are currently unknown; t...
متن کاملCombining modelling and mutagenesis studies of synaptic vesicle protein 2A to identify a series of residues involved in racetam binding.
LEV (levetiracetam), an antiepileptic drug which possesses a unique profile in animal models of seizure and epilepsy, has as its unique binding site in brain, SV2A (synaptic vesicle protein 2A). Previous studies have used a chimaeric and site-specific mutagenesis approach to identify three residues in the putative tenth transmembrane helix of SV2A that, when mutated, alter binding of LEV and re...
متن کاملLevetiracetam Affects Differentially Presynaptic Proteins in Rat Cerebral Cortex
Presynaptic proteins are potential therapeutic targets for epilepsy and other neurological diseases. We tested the hypothesis that chronic treatment with the SV2A ligand levetiracetam affects the expression of other presynaptic proteins. Results showed that in rat neocortex no significant difference was detected in SV2A protein levels in levetiracetam treated animals compared to controls, where...
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ورودعنوان ژورنال:
- Cell
دوره 167 شماره
صفحات -
تاریخ انتشار 2016