Abstract | INTRODUCTION: AREAS COVERED: This drug discovery case history focuses on the discovery and profiling of perampanel. It analyzes the pharmacological, behavioral and molecular mechanisms of perampanel and how they contribute to the therapeutic benefits of the drug. The article is based on the data reported in published preclinical and clinical studies, product labels and poster presentations. EXPERT OPINION: Preclinical studies of perampanel have identified its broad-spectrum antiseizure effects in acute seizure models, with a narrow therapeutic index in the rotarod test similar to other AMPA receptor antagonists. This narrow therapeutic index is a potential problem for AMPA receptor antagonists. However, the discovery that perampanel has a very long half-life in humans, with gradual accumulation in plasma, could contribute to the development of tolerance. This, coupled with the identification of an optimal dosing strategy for individual patients, may help to maximize the utility of perampanel in the treatment of epilepsy.
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Authors | Takahisa Hanada |
Journal | Expert opinion on drug discovery
(Expert Opin Drug Discov)
Vol. 9
Issue 4
Pg. 449-58
(Apr 2014)
ISSN: 1746-045X [Electronic] England |
PMID | 24559052
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Anticonvulsants
- Nitriles
- Pyridones
- Receptors, AMPA
- perampanel
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Topics |
- Animals
- Anticonvulsants
(pharmacokinetics, pharmacology, therapeutic use)
- Epilepsy
(drug therapy, metabolism)
- Humans
- Nitriles
- Pyridones
(pharmacokinetics, pharmacology, therapeutic use)
- Receptors, AMPA
(antagonists & inhibitors, metabolism)
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