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Michael A. Rogawski

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A New Sv2a Ligand For Epilepsy, Michael A. Rogawski Oct 2016

A New Sv2a Ligand For Epilepsy, Michael A. Rogawski

Michael A. Rogawski

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.

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Role Of Gluk1 Kainate Receptors In Seizures, Epileptic Discharges, And Epileptogenesis, Brita Fritsch, Janine Reis, Maciej Gasior, Rafal M. Kaminski, Michael A. Rogawski Apr 2014

Role Of Gluk1 Kainate Receptors In Seizures, Epileptic Discharges, And Epileptogenesis, Brita Fritsch, Janine Reis, Maciej Gasior, Rafal M. Kaminski, Michael A. Rogawski

Michael A. Rogawski

Kainate receptors containing the GluK1 subunit have an impact on excitatory and inhibitory neurotransmission in brain regions, such as the amygdala and hippocampus, which are relevant to seizures and epilepsy. Here we used 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a potent and selective agonist of kainate receptors that include the GluK1 subunit, in conjunction with mice deficient in GluK1 and GluK2 kainate receptor subunits to assess the role of GluK1 kainate receptors in provoking seizures and in kindling epileptogenesis. We found that systemic ATPA, acting specifically via GluK1 kainate receptors, causes locomotor arrest and forelimb extension (a unique behavioral characteristic of GluK1 …

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