Perampanel

Overview

Perampanel, sold under the brand name Fycompa, is an anti-epileptic medication developed by Eisai that is used in addition to other medications to treat partial seizures and generalized tonic–clonic seizures. Perampanel is a non-competitive AMPA glutamate receptor antagonist. It is taken by mouth.[1] WP

Perampanel was approved in 2012, and as of 2016, its optimal role in the treatment of epilepsy relative to other drugs is not clear. It is the first anti-epileptic drug in the class of selective non-competitive antagonist of AMPA receptors.[2][3] WP

The US prescribing information has a boxed warning that perampanel may cause serious psychiatric and behavioral changes; it may cause homicidal or suicidal thoughts. Other side effects have included dizziness, somnolence, vertigo, aggression, anger, loss of coordination, blurred vision, irritability, and slurred speech. Perampanel reduced the effectiveness of levonorgestrel oral contraceptives by about 40%. Women who may get pregnant should not take it as studies in animals show it may harm a fetus. Perampanel is liable to be abused; very high doses produced euphoria responses similar to ketamine. It is designated as a Schedule III controlled substance by the US Drug Enforcement Administration. Perampanel is authorized as a generic medication.[1][4][5] WP

Uses, dosage and effects

Medical uses

Perampanel is used in addition to other drugs to treat partial seizures and generalized tonic–clonic seizures for people older than twelve years.[1] WP

In the US, perampanel is indicated for the treatment of partial-onset seizures with or without secondarily generalized seizures in people with epilepsy aged four years of age and older; and for adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in people with epilepsy aged twelve years of age and older.[1] WP

In the EU, perampanel is indicated for the adjunctive treatment of partial-onset seizures with or without secondarily generalized seizures in people aged twelve years of age and older with epilepsy; and for the adjunctive treatment of primary generalized tonic-clonic seizures in people aged twelve years of age and older with idiopathic generalized epilepsy.[6] WP

Risks and side effects

Contraindications

Based on animal data, perampanel may cause fetal harm; it is not recommended for women of child-bearing age not taking contraception.[1][4] WP

People with severe liver impairment or severe kidney disease, including those on dialysis, should not take perampanel.[1] WP

Side effects

Perampanel's label has a black box warning noting that some people taking the drug have undergone serious psychiatric and behavioral changes. These events occurred in people who had no history of such issues, as well as people who had such a history. The psychiatric changes included mood changes such as euphoria, anger, irritability, aggression, belligerence, agitation, and anxiety, as well as psychosis and delirium. Behavioral changes included physical assault and homicidal ideation or threats.[1] WP

Other serious side effects include suicidal thoughts or behavior, dizziness and gait disturbance, somnolence and fatigue, risk of falls, and increased risk of seizures if the drug is quickly withdrawn.[1] WP

In clinical trials, dizziness, somnolence, vertigo, aggression, anger, loss of coordination, blurred vision, irritability, and slurred speech were the side effects that most commonly led people to leave the trial.[1] WP

Perampanel is liable to be abused: very high doses produced euphoria responses and dissociative effects similar to ketamine, although subjects liked it less and had experienced it more negatively than ketamine. It is designated as a Schedule III controlled substance by the Drug Enforcement Administration. A study of dependence in rats found withdrawal symptoms when the drug was removed; dependence in humans wasn't studied well enough to make generalizations as of April 2016. There is limited experience with overdose.[1] WP

Interactions

Interactions

Perampanel reduced the effectiveness of levonorgestrel oral contraceptives by about 40%. Other antieptilectic drugs that induce cytochrome P450, including carbamazepine, phenytoin, and oxcarbazepine decrease the effectiveness of perampanel by 50-67%. Use of perampanel with strong CYP3A inducers like rifampin or St. John's wort is not recommended. Use of perampanel with CNS depressants like alcohol may increase the effect of the CNS depressant.[1] WP

Pharmacology

Pharmacology

Perampanel is a selective non-competitive antagonist of AMPA receptors, the major subtype of ionotropic glutamate receptors. It was the first drug of this class approved for epilepsy.[3][7][8] WP

Whole-cell voltage clamp studies have demonstrated that perampanel is a negative allosteric AMPA receptor antagonist. Perampanel caused a slow (τ~1 s at 3 μM), concentration-dependent inhibition of AMPA receptor currents. The rates of block and unblock of AMPA receptor currents were 1.5×10⁵ M⁻¹ s⁻¹ and 0.58 s⁻¹, respectively. Perampanel did not affect NMDA receptor currents. The extent of block (IC₅₀, 0.56 μM) was similar at all agonist concentrations, demonstrating a noncompetitive blocking action. Parampanel did affect AMPA receptor desensitization, or the ratio of peak to late response to rapid application of AMPA. Perampanel is a selective negative allosteric AMPA receptor antagonist of high-affinity and slow blocking kinetics, and is not use-dependent.[9] WP

Perampanel has a prolonged terminal half-life in humans of approximately 105 hours. The drug is 95% bound to plasma protein. Its primary route of metabolism is by CYP3A4. It does not induce P450 enzymes. About 70% of the dose is excreted in the feces and 30% in the urine; less than 2% of the dose is excreted unchanged into the urine.[4] WP

Research

Research

A 2016 review found it effective for both indications but due to the newness of the drug was unable to describe its optimal role in the treatment of epilepsy relative to other drugs. A 2014 review of the probability of added benefit of perampanel to the standard of care was unable to come to any conclusions, as no trial conducted by Eisai compared perampanel to a drug within the standard of care, but only to placebo.[2][10] WP

History

History

It was authorized for medical use in the European Union in July 2012, and as of July 2016, was authorized as an adjunct treatment of partial-onset seizures with or without secondarily generalized seizures in people with epilepsy older than twelve years and as an adjunct treatment of primary generalized tonic–clonic seizures for people older than twelve years who have idiopathic generalized epilepsy.[4][6] WP

It was approved for medical use in the United States in October 2012, and then in June 2015, for the same uses as those in the European Union. The oral suspension was approved for medical use in the United States in April 2016.[3][11][12] WP

Chemistry

Formula

C23H15N3O PC

CAS number

380917-97-5 PC

Molar mass (g/mol)

349.4 PC

IUPAC name (computed by PubChem)

2-(2-oxo-1-phenyl-5-pyridin-2-yl-3-pyridinyl)benzonitrile PC

SMILES

C1=CC=C(C=C1)N2C=C(C=C(C2=O)C3=CC=CC=C3C#N)C4=CC=CC=N4 PC

InChIKey

PRMWGUBFXWROHD-UHFFFAOYSA-N PC

PubChem CID

9924495

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Fycompa- perampanel tablet Fycompa- perampanel suspension
2. Journal / agency Besag FM, Patsalos PN. Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures. Neuropsychiatric Disease and Treatment. 2016. doi:10.2147/NDT.S83842 · PMID 27274257 · PMC4876101
3. Journal / agency Chong DJ, Lerman AM. Practice Update: Review of Anticonvulsant Therapy. Current Neurology and Neuroscience Reports. April 2016. doi:10.1007/s11910-016-0640-y · PMID 26984292
4. Journal / agency Index pagel. 17 September 2018
5. Other Generic Fycompa Availability. 10 September 2025
6. Journal / agency Fycompa EPAR. 23 April 2018
7. Journal / agency Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Currents. March 2011. doi:10.5698/1535-7511-11.2.56 · PMID 21686307 · PMC3117497
8. Journal / agency Rogawski MA, Hanada T. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurologica Scandinavica. Supplementum. 2013. doi:10.1111/ane.12100 · PMID 23480152 · PMC4506647
9. Journal / agency Chen CY, Matt L, Hell JW, Rogawski MA. Perampanel inhibition of AMPA receptor currents in cultured hippocampal neurons. PLOS ONE. 17 September 2014. doi:10.1371/journal.pone.0108021 · PMID 25229608 · PMC4168215
10. Journal / agency Institute for Quality Efficiency in Health Care. Perampanel -- Benefit Assessment According to §35a Social Code Book V [Internet]. Extract of Dossier Assessment No. A14-16. IQWiG Dossier Assessment Extracts. 13 August 2014. PMID 26677496
11. Journal / agency Drug Approval Package: Fycompa (perampanel) Tablets NDA #202834. 28 November 2012
12. Journal / agency Fycompa (perampanel) Oral Suspension. 27 November 2017

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.