Revisiting AMPA Receptors as an Antiepileptic Drug Target

@article{Rogawski2011RevisitingAR,
  title={Revisiting AMPA Receptors as an Antiepileptic Drug Target},
  author={Michael A. Rogawski},
  journal={Epilepsy Currents},
  year={2011},
  volume={11},
  pages={56 - 63}
}
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… Expand
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The role of AMPA receptors in the neuronal hyperexcitability underlying epilepsy, the mechanism of action and clinical experience on the anti-seizure activity of perampanel, and the rationale for targeting AMPA receptor in specific epileptic disorders are evaluated. Expand
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The field of AMPAR ligands continues to be a dynamic area of drug discovery, with a pronounced diversification of the chemotypes explored as positive allosteric modulators in recent years. Expand
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The development of AMPAR antagonists confirms their great clinical potential and their arrival to clinical practice has been slowed down by their unfavorable pharmacokinetic profile and tolerability; however, their clinical use might be justified by their efficacy and the new drugs developed such as perampanel have been greatly ameliorated from both points of view. Expand
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The data raised from the studies can give a hope that perampanel offers a valuable option as an adjuvant therapy for pharmacoresistant partial-onset and secondarily generalized seizures. Expand
The AMPA receptor antagonist perampanel is a new hope in the treatment for epilepsy
TLDR
The data raised from the studies can give a hope that perampanel offers a valuable option as an adjuvant therapy for pharmacoresistant partial‐onset and secondarily generalized seizures. Expand
Research advances in basic mechanisms of seizures and antiepileptic drug action.
TLDR
Development of ideas on the mechanisms of seizures and antiepileptic drugs reflects the progress in the understanding of the central nervous system physiology, particularly of neurotransmission, and an emerging role of extrasynaptic GABAA receptors, various kinds of potassium ion channels, hyperpolarization-activated cyclic nucleotide gated (HCN) channels, acid-sensing ions channels, and gap junctions in the regulation of neuronal excitability and seizures are presented. Expand
The AMPA receptor antagonist perampanel in the adjunctive treatment of partial-onset seizures: clinical trial evidence and experience
  • B. Steinhoff
  • Medicine
  • Therapeutic advances in neurological disorders
  • 2015
TLDR
Perampanel is the first-in-class orally active, selective, noncompetitive antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the pharmacokinetic profile offers once-daily dosing in the evening as the best route of administration. Expand
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