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- Antiepileptic drug (4)
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Articles 1 - 8 of 8
Full-Text Articles in Medical Neurobiology
Rapid Quantitative Pharmacodynamic Imaging By A Novel Method: Theory, Simulation Testing And Proof Of Principle, Kevin J. Black, Jonathan M. Koller, Brad D. Miller
Rapid Quantitative Pharmacodynamic Imaging By A Novel Method: Theory, Simulation Testing And Proof Of Principle, Kevin J. Black, Jonathan M. Koller, Brad D. Miller
Kevin J. Black, MD
Pharmacological challenge imaging has mapped, but rarely quantified, the sensitivity of a biological system to a given drug. We describe a novel method called rapid quantitative pharmacodynamic imaging. This method combines pharmacokinetic-pharmacodynamic modeling, repeated small doses of a challenge drug over a short time scale, and functional imaging to rapidly provide quantitative estimates of drug sensitivity including EC50 (the concentration of drug that produces half the maximum possible effect). We first test the method with simulated data, assuming a typical sigmoidal dose-response curve and assuming imperfect imaging that includes artifactual baseline signal drift and random error. With these few assumptions, …
Antiepileptic Drugs And Migraine, Michael Rogawski
Antiepileptic Drugs And Migraine, Michael Rogawski
Michael A. Rogawski
Prepared for the 16th International Headache Research Seminar, “Innovative Drug Development For Headache Disorders,” March 23–25, 2007, Copenhagen, Denmark.
Brivaracetam: A Rational Drug Discovery Success Story, Michael Rogawski
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 …
Common Pathophysiologic Mechanisms In Migraine And Epilepsy, Michael A. Rogawski
Common Pathophysiologic Mechanisms In Migraine And Epilepsy, Michael A. Rogawski
Michael A. Rogawski
Migraine and epilepsy are comorbid episodic disorders that have common pathophysiologic mechanisms. Migraine attacks, like epileptic seizures, may be triggered by excessive neocortical cellular excitability; in migraine, however, the hyperexcitability is believed to transition to cortical spreading depression rather than to the hypersynchronous activity that characterizes seizures. Some forms of epilepsy and migraine are known to be channelopathies. Mutations in the same genes can cause either migraine or epilepsy or, in some cases, both. Given the likely commonalities in the underlying cellular and molecular mechanisms, it is not surprising that some antiepileptic drugs, including valproate, topiramate, and gabapentin, are effective …
Molecular Targets For Antiepileptic Drug Development, Brian S. Meldrum, Michael A. Rogawski
Molecular Targets For Antiepileptic Drug Development, Brian S. Meldrum, Michael A. Rogawski
Michael A. Rogawski
This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the alpha subunits of voltage-gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently, alpha2-delta voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na+ …
The Neurobiology Of Antiepileptic Drugs For The Treatment Of Nonepileptic Conditions, Michael A. Rogawski, Wolfgang Löscher
The Neurobiology Of Antiepileptic Drugs For The Treatment Of Nonepileptic Conditions, Michael A. Rogawski, Wolfgang Löscher
Michael A. Rogawski
Antiepileptic drugs (AEDs) are commonly prescribed for nonepileptic conditions, including migraine headache, chronicneuropathic pain, mood disorders, schizophrenia and various neuromuscular syndromes. In many of these conditions, as in epilepsy, the drugs act by modifying the excitability of nerve (or muscle) through effects on voltage-gated sodium and calciumchannels or by promoting inhibition mediated by γ-aminobutyric acid (GABA) A receptors. In neuropathic pain, chronic nerveinjury is associated with the redistribution and altered subunit compositions of sodium and calcium channels that predisposeneurons in sensory pathways to fire spontaneously or at inappropriately high frequencies, often from ectopic sites. AEDs maycounteract this abnormal activity by …
The Neurobiology Of Antiepileptic Drugs, Michael Rogawski, Wolfgang Löscher
The Neurobiology Of Antiepileptic Drugs, Michael Rogawski, Wolfgang Löscher
Michael A. Rogawski
Antiepileptic drugs (AEDs) provide satisfactory control of seizures for most patients with epilepsy. The drugs have the remarkable ability to protect against seizures while permitting normal functioning of the nervous system. AEDs act on diverse molecular targets to selectively modify the excitability of neurons so that seizure-related firing is blocked without disturbing non-epileptic activity. This occurs largely through effects on voltage-gated sodium and calcium channels, or by promoting inhibition mediated by GABA-A (γ-aminobutyric acid, type A) receptors. The subtle biophysical modifications inchannel behaviour that are induced by AEDs are often functionally opposite to defects in channel properties that are caused …
Neurosteroids: Endogenous Modulators Of Seizure Susceptibility, Michael A. Rogawski, Doodipala S. Reddy
Neurosteroids: Endogenous Modulators Of Seizure Susceptibility, Michael A. Rogawski, Doodipala S. Reddy
Michael A. Rogawski
No abstract provided.