Perampanel

Identification

Summary

Perampanel is a non-competitive AMPA glutamate receptor antagonist used to treat partial-onset seizures with or without secondarily generalized seizures, and as adjunctive treatment of primary generalized tonic-clonic seizures in patients with epilepsy.

Brand Names
Fycompa
Generic Name
Perampanel
DrugBank Accession Number
DB08883
Background

Perampanel is a noncompetitive AMPA glutamate receptor antagonist. It is marketed under the name Fycompa™ and is indicated as an adjunct in patients over 12 years old for the treatment of partial-onset seizures that may or may not occur with generalized seizures. The FDA label includes an important black-boxed warning of serious or life-threatening behavioral and psychiatric reactions in patients taking Fycompa™.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 349.393
Monoisotopic: 349.121512115
Chemical Formula
C23H15N3O
Synonyms
  • 3-(2-Cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one
  • Perampanel
  • Pérampanel
  • Perampanelum
External IDs
  • E-2007
  • E2007
  • ER-155055-90

Pharmacology

Indication

Used in patients over 12 years old for the treatment of partial-onset seizures that may or may not occur with generalized seizures.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Perampanel is involved in inhibiting neuronal excitation in the central nervous system leading to such effects as decreased pyschomotor performance.

Mechanism of action

The exact mechanism of action of perampanel in seizures is not yet determined, but it is known that perampanel decreases neuronal excitation by non-competitive ihibition of the AMPA receptor.

TargetActionsOrganism
AGlutamate receptor 1
antagonist
Humans
Absorption

After oral adminitration, perampanel is absorbed rapidly and completely.

Volume of distribution

The volume of distribution of perampanel was not quantified.

Protein binding

Perampanel is 95-96% plasma protein bound with most binding to the plasma proteins α1-acid glycoprotein and albumin.

Metabolism

Perampanel is highly metabolized by CYP3A4 and/or CYP3A5 primary oxidation and by sequential glucuronidation.

Route of elimination

Perampanel is eliminated mostely in the feces (48%) and to a lesser exten in the urine (22%).

Half-life

Perampanel has a long elmination half-life of about 105 hours.

Clearance

In healthy patients, perampanel has a clearance of about 12 mL/min.

Adverse Effects
Adverseeffects
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Toxicity

The FDA label includes an important warning of serious or life-threatening behavioral and psychiatric adverse reactions including aggression, hostility, irritability, anger, and homicidal thoughts in patients taking perampanel.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepinePerampanel may increase the central nervous system depressant (CNS depressant) activities of 1,2-Benzodiazepine.
AbametapirThe serum concentration of Perampanel can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Perampanel can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Perampanel.
AbirateroneThe serum concentration of Perampanel can be increased when it is combined with Abiraterone.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Perampanel.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Perampanel.
AcetaminophenThe metabolism of Perampanel can be increased when combined with Acetaminophen.
AcetazolamidePerampanel may increase the central nervous system depressant (CNS depressant) activities of Acetazolamide.
AcetophenazinePerampanel may increase the central nervous system depressant (CNS depressant) activities of Acetophenazine.
Interactions
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Food Interactions
  • Take with or without food. Food slows the rate of absorption but not the extent.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Perampanel hydrate8LIX22217M1571982-04-1PDWMJDKMSASBNE-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FycompaSuspension0.5 mg/mlOralEisai Limited2020-12-21Not applicableEU flag
FycompaTablet10.0 mgOralEisai Limited2013-06-03Not applicableCanada flag
FycompaTablet, film coated8 mgOralEisai Limited2016-09-07Not applicableEU flag
FycompaTablet, film coated8 mgOralEisai Limited2016-09-07Not applicableEU flag
FycompaTablet4.0 mgOralEisai Limited2013-06-19Not applicableCanada flag
FycompaTablet, film coated6 mgOralEisai Limited2016-09-07Not applicableEU flag
FycompaSuspension0.5 mg/1mLOralEisai Inc.2016-04-30Not applicableUS flag
FycompaTablet, film coated2 mgOralEisai Limited2016-09-07Not applicableEU flag
FycompaTablet, film coated4 mgOralEisai Limited2016-09-07Not applicableEU flag
FycompaTablet, film coated12 mgOralEisai Limited2016-09-07Not applicableEU flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
FycompaPerampanel (2 mg/1) + Perampanel (4 mg/1)KitOralEisai Inc.2012-10-222012-10-15US flag
FycompaPerampanel (2 mg/1) + Perampanel (4 mg/1)KitOralEisai Inc.2012-10-222012-10-15US flag

Categories

ATC Codes
N03AX22 — Perampanel
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as bipyridines and oligopyridines. These are organic compounds containing two pyridine rings linked to each other.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Bipyridines and oligopyridines
Direct Parent
Bipyridines and oligopyridines
Alternative Parents
Phenylpyridines / Benzonitriles / Pyridinones / Dihydropyridines / Heteroaromatic compounds / Lactams / Nitriles / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds
show 2 more
Substituents
3-phenylpyridine / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Benzonitrile / Bipyridine / Carbonitrile / Dihydropyridine / Heteroaromatic compound / Hydrocarbon derivative
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
nitrile, pyridone, bipyridines (CHEBI:71013)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
H821664NPK
CAS number
380917-97-5
InChI Key
PRMWGUBFXWROHD-UHFFFAOYSA-N
InChI
InChI=1S/C23H15N3O/c24-15-17-8-4-5-11-20(17)21-14-18(22-12-6-7-13-25-22)16-26(23(21)27)19-9-2-1-3-10-19/h1-14,16H
IUPAC Name
2-{6'-oxo-1'-phenyl-1',6'-dihydro-[2,3'-bipyridine]-5'-yl}benzonitrile
SMILES
O=C1N(C=C(C=C1C1=CC=CC=C1C#N)C1=NC=CC=C1)C1=CC=CC=C1

References

Synthesis Reference

Francesco Fontana, "METHODS FOR PREPARING INTERMEDIATES OF PERAMPANEL." U.S. Patent US20130109862, issued May 02, 2013.

US20130109862
General References
  1. Hanada T, Hashizume Y, Tokuhara N, Takenaka O, Kohmura N, Ogasawara A, Hatakeyama S, Ohgoh M, Ueno M, Nishizawa Y: Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia. 2011 Jul;52(7):1331-40. doi: 10.1111/j.1528-1167.2011.03109.x. Epub 2011 Jun 2. [Article]
KEGG Drug
D08964
PubChem Compound
9924495
PubChem Substance
347827808
ChemSpider
8100130
BindingDB
50184410
RxNav
1356552
ChEBI
71013
ChEMBL
CHEMBL1214124
ZINC
ZINC000030691797
PDBe Ligand
6ZP
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Perampanel
PDB Entries
5l1f
FDA label
Download (611 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentEpilepsies1
4CompletedTreatmentEpilepsies1
4CompletedTreatmentGrand mal Generalized tonic-clonic seizure / Partial-Onset Seizures / Secondarily Generalized Seizures1
4CompletedTreatmentPrimary Brain Tumors1
4Not Yet RecruitingTreatmentEpilepsies1
4RecruitingPreventionEpilepsy, Intractable / Gliomas, Malignant / Seizures Disorders1
4RecruitingTreatmentEpilepsies / Seizures1
4RecruitingTreatmentHealthy Subjects (HS)1
4TerminatedTreatmentEpilepsies1
4Unknown StatusNot AvailableElectroencephalography1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
KitOral
SuspensionOral0.5 mg / mL
SuspensionOral0.5 mg/1mL
SuspensionOral0.5 MG/ML
TabletOral10 mg/1
TabletOral10.0 mg
TabletOral12 mg/1
TabletOral12.0 mg
TabletOral2 mg/1
TabletOral2.0 mg
TabletOral4 mg/1
TabletOral4.0 mg
TabletOral6 mg/1
TabletOral6.0 mg
TabletOral8 mg/1
TabletOral8.0 mg
Tablet, film coatedOral
Tablet, film coatedOral10 MG
Tablet, film coatedOral12 MG
Tablet, film coatedOral2 MG
Tablet, film coatedOral4 MG
Tablet, film coatedOral6 MG
Tablet, film coatedOral8 MG
Tablet, coatedOral2 mg
Tablet, coatedOral4 mg
Tablet, coatedOral8 mg
Tablet, coatedOral12 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6949571No2005-09-272021-06-08US flag
US8772497No2014-07-082026-05-16US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insoluble in water.From FDA label.
Predicted Properties
PropertyValueSource
Water Solubility0.0056 mg/mLALOGPS
logP3.54ALOGPS
logP4.11ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)4.01ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area56.99 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity104.74 m3·mol-1ChemAxon
Polarizability38.03 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Pdz domain binding
Specific Function
Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a co...
Gene Name
GRIA1
Uniprot ID
P42261
Uniprot Name
Glutamate receptor 1
Molecular Weight
101505.245 Da
References
  1. Hanada T, Hashizume Y, Tokuhara N, Takenaka O, Kohmura N, Ogasawara A, Hatakeyama S, Ohgoh M, Ueno M, Nishizawa Y: Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia. 2011 Jul;52(7):1331-40. doi: 10.1111/j.1528-1167.2011.03109.x. Epub 2011 Jun 2. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Patsalos PN: The clinical pharmacology profile of the new antiepileptic drug perampanel: A novel noncompetitive AMPA receptor antagonist. Epilepsia. 2015 Jan;56(1):12-27. doi: 10.1111/epi.12865. Epub 2014 Dec 13. [Article]
  2. Fycompa (Perampanel) FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Fycompa (Perampanel) FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Greenwood J, Valdes J: Perampanel (Fycompa): A Review of Clinical Efficacy and Safety in Epilepsy. P T. 2016 Nov;41(11):683-698. [Article]
  2. Perampanel FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Fycompa (Perampanel) FDA Label [Link]

Drug created on May 22, 2013 01:44 / Updated on September 27, 2021 07:54