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Neuroscience and Neurobiology

Commentaries and Editorials

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Full-Text Articles in Medical Neurobiology

The Intrinsic Severity Hypothesis Of Pharmacoresistance To Antiepileptic Drugs, Michael Rogawski Dec 2012

The Intrinsic Severity Hypothesis Of Pharmacoresistance To Antiepileptic Drugs, Michael Rogawski

Michael A. Rogawski

Pharmacoresistance to antiepileptic drugs (AEDs) is a barrier to seizure freedom for many persons with epilepsy. For nearly two decades, pharmacoresistance has been framed in terms of factors affecting the access of AEDs to their molecular targets in the brain or the actions of the drugs on these targets. Shortcomings in this prevailing view led to the formulation of the intrinsic severity hypothesis of pharmacoresistance to AEDs, which is based on the recognition that there are neurobiologic factors that confer phenotypic variation among individuals with etiologically similar forms of epilepsy and postulates that more severe epilepsy is more difficult to …


Disclosure Of Clinical Trial Results When Product Development Is Abandoned, Michael A. Rogawski, Howard J. Federoff Sep 2011

Disclosure Of Clinical Trial Results When Product Development Is Abandoned, Michael A. Rogawski, Howard J. Federoff

Michael A. Rogawski

Currently, sponsors are not required to report the outcomes of clinical research on drugs or devices that do not lead to an approved product. Consequently, the public cannot benefit from scientific information derived from all failed or abandoned drugs and devices. Provisions in the U.S. Food and Drug Administration Amendments Act of 2007 provide an opportunity for the Department of Health and Human Services to rectify this situation. By reporting the results of clinical trials of abandoned products in a publicly accessible database and in the peer-reviewed journal literature, sponsors would satisfy a core ethical obligation of clinical research and …


Neurosteroids On The Epilepsy Chessboard — Keeping Seizures In Check, Michael A. Rogawski Dec 2009

Neurosteroids On The Epilepsy Chessboard — Keeping Seizures In Check, Michael A. Rogawski

Michael A. Rogawski

No abstract provided.


Nontraditional Epilepsy Treatment Approaches, Michael A. Rogawski, Gregory L. Holmes Mar 2009

Nontraditional Epilepsy Treatment Approaches, Michael A. Rogawski, Gregory L. Holmes

Michael A. Rogawski

Overview of articles published in a special issue of Neurotherapeutics (April 2009) on nontraditional (non-drug) epilepsy treatment approaches. From the Fourth Workshop on New Horizons in the Development of Antiepileptic Drugs: Nontraditional Approaches to Treat Epilepsy, which was held at the Clontarf Castle, Dublin, March 5-7, 2008.


Brivaracetam: A Rational Drug Discovery Success Story, Michael Rogawski Jan 2008

Brivaracetam: A Rational Drug Discovery Success Story, Michael Rogawski

Michael A. Rogawski

Levetiracetam, the alpha-ethyl analogue of the nootropic piracetam, is a widely used antiepileptic drug (AED) that provides protection against partial seizures and is also effective in the treatment of primary generalized seizure syndromes including juvenile myoclonic epilepsy. Levetiracetam was discovered in 1992 through screening in audiogenic seizure susceptible mice and, 3 years later, was reported to exhibit saturable, stereospecific binding in brain to a approximately 90 kDa protein, later identified as the ubiquitous synaptic vesicle glycoprotein SV2A. A large-scale screening effort to optimize binding affinity identified the 4-n-propyl analogue, brivaracetam, as having greater potency and a broadened spectrum of activity …