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Neurotransmitters and pharmacology
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
Ronald A. Browning, Richard W. Clough
As indicated previously, there is a recently marketed noncompetitive antagonist of the AMPA glutamate receptor (i.e., perampanel, Fycompa®) that is used to treat partial onset seizures with or without secondary generalization. This represents a novel mechanism of action for antiepileptic drugs, and we are likely to see more drugs in this category in the future. Perampanel is well-tolerated by patients but has a number of interactions with other drugs.
Safety evaluation of perampanel as monotherapy or first adjunctive therapy in patients with epilepsy
Published in Expert Opinion on Drug Safety, 2022
James Wheless, Nitish Chourasia
There are limited data available for safety of perampanel in pregnancy [38,39]. As of August 2018, 96 pregnancies were reported to have had perampanel exposure: 43 were known to result in normal live births, 28 did not reach full-term, 18 were lost to follow-up, and seven were ongoing at data cutoff [38]. Preclinical data suggest perampanel exposure during pregnancy could potentially lead to diverticulum of the intestine, delays in aspects of physical development, and pregnancy loss [38]. Thus, pregnant women taking perampanel should be carefully monitored (including drug-level monitoring, if available, since dose adjustments may be needed to maintain consistent exposure) and encouraged to enroll in a pregnancy registry to allow more data to be collected in this population [5,38].
Clinical effects and outcomes of perampanel overdoses reported to U.S. poison centers
Published in Clinical Toxicology, 2022
Faisal Syed Minhaj, James B. Leonard, Wendy Klein-Schwartz
Perampanel is a newer antiepileptic agent that was approved in the United States in 2012 for use in adults with partial onset seizures [1]. The mechanism of action for perampanel is unique among antiepileptic agents as it inhibits glutamate activity on AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Glutamate is the primary excitatory neurotransmitter in the central nervous system acting on AMPA glutamate receptors. Perampanel is thought to antagonize this receptor and decrease the overstimulation that can occur with seizure activity, leading to decreased signal transmission. Currently, there are few published case reports describing acute overdose [2–5]. Reported symptoms include prolonged central nervous system depression, respiratory depression, and aggressive behavior requiring chemical and physical restraints. Recently, approval was expanded for more seizure disorders and for use in the pediatric population, potentially increasing availability.
ALSUntangled 48: Perampanel (Fycompa)
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2019
Perampanel is a drug currently used to treat seizures which has a mechanism of action that theoretically could be useful in treating patients with ALS. A single flawed study in a mouse model of ALS showed some benefits of perampanel, but data from humans with ALS is quite limited. Due to the lack of data in PALS, the failure of the closely related drug talampanel in ALS clinical trials, and several serious safety concerns, including an increased fall risk and serious psychiatric adverse effects, we cannot recommend off-label use of perampanel for ALS at this time. We look forward to the results of the on-going clinical trials of perampanel in ALS and we will update our TOE grades accordingly when these results become available.