Identification

Name
Perampanel
Accession Number
DB08883
Type
Small Molecule
Groups
Approved
Description

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™.

Structure
Thumb
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
Product Ingredients
IngredientUNIICASInChI Key
Perampanel hydrate8LIX22217M1571982-04-1PDWMJDKMSASBNE-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FycompaTablet, film coated10 mgOralEisai Europe Ltd2012-07-23Not applicableEu
FycompaSuspension0.5 mgOralEisai LimitedNot applicableNot applicableCanada
FycompaTablet6.0 mgOralEisai Limited2013-06-19Not applicableCanada
FycompaTablet, film coated8 mgOralEisai Europe Ltd2012-07-23Not applicableEu
FycompaTablet, film coated8 mgOralEisai Europe Ltd2012-07-23Not applicableEu
FycompaTablet2.0 mgOralEisai Limited2013-06-19Not applicableCanada
FycompaSuspension0.5 mg/1mLOralEisai Inc.2016-04-30Not applicableUs
FycompaTablet, film coated6 mgOralEisai Europe Ltd2012-07-23Not applicableEu
FycompaTablet, film coated4 mgOralEisai Europe Ltd2012-07-23Not applicableEu
FycompaTablet, film coated12 mgOralEisai Europe Ltd2012-07-23Not applicableEu
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
FycompaPerampanel (2 mg/1) + Perampanel (4 mg/1)KitEisai Inc.2012-10-222012-10-15Us
FycompaPerampanel (2 mg/1) + Perampanel (4 mg/1)KitEisai Inc.2012-10-222012-10-15Us
Categories
UNII
H821664NPK
CAS number
380917-97-5
Weight
Average: 349.393
Monoisotopic: 349.121512115
Chemical Formula
C23H15N3O
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

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.

Associated Conditions
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
Human
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.

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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Perampanel.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Perampanel.
2,5-Dimethoxy-4-ethylthioamphetaminePerampanel may increase the central nervous system depressant (CNS depressant) activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Perampanel.
3,4-MethylenedioxyamphetaminePerampanel may increase the central nervous system depressant (CNS depressant) activities of 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Perampanel.
4-Bromo-2,5-dimethoxyamphetaminePerampanel may increase the central nervous system depressant (CNS depressant) activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Perampanel.
4-MethoxyamphetaminePerampanel may increase the central nervous system depressant (CNS depressant) activities of 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Perampanel.
Food Interactions
  • Food slows perampanel's absorption rate but not extent.

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. [PubMed:21635236]
External Links
KEGG Drug
D08964
PubChem Compound
9924495
PubChem Substance
347827808
ChemSpider
8100130
BindingDB
50184410
ChEBI
71013
ChEMBL
CHEMBL1214124
HET
6ZP
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Perampanel
ATC Codes
N03AX22 — Perampanel
AHFS Codes
  • 28:12.92 — Miscellaneous Anticonvulsants
PDB Entries
5l1f
FDA label
Download (611 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Participants2
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentCentral Nervous System1
1CompletedTreatmentHealthy Volunteers5
1CompletedTreatmentPartial Onset Epilepsy2
1Not Yet RecruitingBasic ScienceMajor Depressive Disorder (MDD)1
1, 2RecruitingTreatmentCervical Dystonia1
2Active Not RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2Active Not RecruitingTreatmentSmall Fibre Neuropathy1
2Active Not RecruitingTreatmentTremor, Essential1
2CompletedNot AvailableParkinson's Disease (PD)1
2CompletedTreatmentCentral Nervous System1
2CompletedTreatmentEpilepsies3
2CompletedTreatmentParkinson's Disease (PD)1
2CompletedTreatmentRefractory Partial Seizures2
2CompletedTreatmentNeurocostal neuralgia1
2CompletedTreatmentProphylaxis of migraine headaches1
2RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2RecruitingTreatmentEpilepsies1
2SuspendedTreatmentAlcohol Dependence1
2TerminatedTreatmentParkinson's Disease (PD)3
2Unknown StatusTreatmentEpilepsies1
2WithdrawnTreatmentParkinson's Disease (PD)1
2, 3CompletedTreatmentDiabetic Neuropathies1
2, 3CompletedTreatmentNeurocostal neuralgia1
3Active Not RecruitingTreatmentPartial-Onset or Primary Generalized Tonic-Clonic Seizures1
3Active Not RecruitingTreatmentPartial onset seizure Epilepsy1
3CompletedTreatmentEpilepsies2
3CompletedTreatmentParkinson's Disease (PD)2
3CompletedTreatmentRefractory Partial Seizures3
3CompletedTreatmentSeizure Disorder Generalized Tonic Clonic1
3RecruitingTreatmentLennox-Gastaut Syndrome (LGS)1
3RecruitingTreatmentPartial onset seizure Epilepsy1
3TerminatedTreatmentParkinson's Disease (PD)3
4Active Not RecruitingTreatmentEpilepsies1
4CompletedTreatmentPrimary Brain Tumors1
4RecruitingNot AvailableElectroencephalography1
4RecruitingTreatmentEpilepsies1
4RecruitingTreatmentHealthy Volunteers1
4RecruitingTreatmentPartial onset seizure Epilepsy / Primary Generalized tonic-clonic seizure / Secondarily Generalized Seizures1
4TerminatedTreatmentEpilepsies1
4WithdrawnTreatmentEpilepsy, Localization Related1
Not AvailableAvailableNot AvailableSeizure Disorder Generalized Tonic Clonic1
Not AvailableAvailableNot AvailablePartial onset seizure Epilepsy1
Not AvailableCompletedNot AvailableEpilepsies1
Not AvailableCompletedNot AvailableRefractory Epilepsy1
Not AvailableNot Yet RecruitingTreatmentRefractory Epilepsy1
Not AvailableRecruitingNot AvailableEpilepsies1
Not AvailableRecruitingNot AvailableEpilepsy, Generalized / Epilepsy, Localization Related / Partial Seizures, Simple1
Not AvailableRecruitingNot AvailablePartial Seizures (With or Without Secondary Generalized Seizures) / Primary Generalized tonic-clonic seizure2
Not AvailableRecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit
SuspensionOral0.5 mg/1mL
SuspensionOral0.5 mg
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 coatedOral10 mg
Tablet, film coatedOral12 mg
Tablet, film coatedOral2 mg
Tablet, film coatedOral4 mg
Tablet, film coatedOral6 mg
Tablet, film coatedOral8 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6949571No2005-09-272021-06-08Us
US8772497No2014-07-082026-05-16Us

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

Taxonomy

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
Bipyridine / 3-phenylpyridine / Benzonitrile / Dihydropyridine / Pyridinone / Monocyclic benzene moiety / Hydropyridine / Benzenoid / Heteroaromatic compound / Lactam
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
nitrile, pyridone, bipyridines (CHEBI:71013)

Targets

Kind
Protein
Organism
Human
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. [PubMed:21635236]

Enzymes

Kind
Protein
Organism
Human
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. [PubMed:25495693]
  2. Fycompa (Perampanel) FDA Label [Link]
Kind
Protein
Organism
Human
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
Human
Pharmacological action
Unknown
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. [PubMed:27904300]
  2. Perampanel FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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 21, 2013 19:44 / Updated on November 17, 2018 07:22