Revisiting AMPA Receptors as an Antiepileptic Drug Target
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TLDR
Promising clinical studies with AMPA receptor antagonists, including the potent noncompetitive antagonist perampanel, are once again focusing attention on AMPA receptors as a drug target for epilepsy therapy.Abstract:
In the 1990s there was intense interest in ionotropic glutamate receptors as therapeutic targets for diverse neurological disorders, including epilepsy. NMDA receptors were thought to play a key role in the generation of seizures, leading to clinical studies of NMDA receptor blocking drugs in epilepsy. Disappointing results dampened enthusiasm for ionotropic glutamate receptors as a therapeutic target. Eventually it became appreciated that another type of ionotropic glutamate receptor, the AMPA receptor, is actually the predominant mediator of excitatory neurotransmission in the central nervous system and moreover that AMPA receptors are critical to the generation and spread of epileptic activity. As drugs became available that selectively target AMPA receptors, it was possible to demonstrate that AMPA receptor antagonists have powerful antiseizure activity in in vitro and in vivo models. A decade later, promising clinical studies with AMPA receptor antagonists, including the potent noncompetitive antagon...read more
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Adjunctive perampanel for refractory partial-onset seizures: Randomized phase III study 304
Jacqueline A. French,Gregory L. Krauss,Victor Biton,David Squillacote,Haichen Yang,Antonio Laurenza,Dinesh Kumar,Michael A. Rogawski +7 more
TL;DR: This trial demonstrated that once-daily, adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures.
Journal ArticleDOI
Randomized phase III study 306 Adjunctive perampanel for refractory partial-onset seizures
Gregory L. Krauss,José M. Serratosa,Vicente Villanueva,M. Endziniene,Z. Hong,Jacqueline A. French,Haichen Yang,David Squillacote,H. B. Edwards,Jin Zhu,Antonio Laurenza +10 more
TL;DR: This trial demonstrated that adjunctive perampanel effectively reduced seizure frequency and possessed a favorable tolerability profile in patients ≥12 years with partial-onset seizures (with or without secondary generalization), with a minimum effective dose of 4 mg/day.
Journal ArticleDOI
Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305.
Jacqueline A. French,Gregory L. Krauss,Bernhard J. Steinhoff,David Squillacote,Haichen Yang,Dinesh Kumar,Antonio Laurenza +6 more
TL;DR: To assess the efficacy and safety of once‐daily doses of perampanel 8 and 12 mg when added to 1–3 concomitantly administered, approved antiepileptic drugs (AEDs) in patients with uncontrolled partial‐onset seizures.
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The Pharmacology of l-DOPA-Induced Dyskinesia in Parkinson’s Disease
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Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders.
Katrin Augustin,Aziza Khabbush,Sophie Williams,Simon Eaton,Michael Orford,J. Helen Cross,Simon Heales,Matthew C. Walker,Robin S.B. Williams +8 more
TL;DR: High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy and the mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes.
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