Details
Stereochemistry | ACHIRAL |
Molecular Formula | C23H15N3O |
Molecular Weight | 349.3847 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O=C1N(C=C(C=C1C2=CC=CC=C2C#N)C3=CC=CC=N3)C4=CC=CC=C4
InChI
InChIKey=PRMWGUBFXWROHD-UHFFFAOYSA-N
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
Molecular Formula | C23H15N3O |
Molecular Weight | 349.3847 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.eisai.com/news/news201551.html; http://www.deadiversion.usdoj.gov/fed_regs/rules/2013/fr1022_8.htm; http://www.ncbi.nlm.nih.gov/pubmed/?term=24421482;
Curator's Comment: description was created based on several sources, including
http://www.eisai.com/news/news201551.html; http://www.deadiversion.usdoj.gov/fed_regs/rules/2013/fr1022_8.htm; http://www.ncbi.nlm.nih.gov/pubmed/?term=24421482;
Perampanel (trade name Fycompa) is an antiepileptic drug developed by Eisai Co. that acts as a selective non-competitive antagonist of AMPA receptors, the major subtype of ionotropic glutamate receptors. Although the mechanism of action through which perampanel exerts its antiepileptic effect has not been fully elucidated, this agent antagonizes the AMPA subtype of the excitatory glutamate receptor found on postsynaptic neurons in the central nervous system (CNS). This antagonistic action prevents AMPA receptor activation by glutamate and results in the inhibition of neuronal excitation, repetitive neuronal firing, and the stabilization of hyper-excited neural membranes. Glutamate, the primary excitatory neurotransmitter in the CNS, plays an important role in various neurological disorders caused by neuronal hyperexcitation. The drug is currently approved, for the control of partial-onset seizures, in those of both sexes who suffer from epilepsy and who are 12 years of age and older, by the Food and Drug Administration. Perampanel is also approved for the treatment of primary generalized tonic-clonic seizures in patients with epilepsy aged 12 years and older. It is designated as a Schedule III controlled substance by the Drug Enforcement Administration. Perampanel has been studied in other clinical indications including Parkinson's disease.
CNS Activity
Sources: http://www.ncbi.nlm.nih.gov/pubmed/26306919
Curator's Comment: Cross the blood-brain barrier in in vitro ischemia model in murine brain endothelial cells.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2096670 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | FYCOMPA Approved UseIndicated as adjunctive therapy for the treatment of Partial-Onset Seizures with or without secondarily generalized seizures in patients with epilepsy 12 years of age and older; Primary Generalized Tonic-Clonic Seizures in patients with epilepsy 12 years of age and older Launch Date2012 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
371.9 μg/L |
4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PERAMPANEL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
123.3 μg/L |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
PERAMPANEL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7352 μg × h/L |
4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PERAMPANEL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8.092 μg × h/L |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
PERAMPANEL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
98.1 h |
4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PERAMPANEL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
117.4 h |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
PERAMPANEL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.5% |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
PERAMPANEL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
10 mg single, oral Overdose |
healthy, 2 years n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 Sources: |
Other AEs: Drowsiness, Ataxia... |
2 mg single, oral Overdose |
healthy, 2 years n = 1 Health Status: healthy Age Group: 2 years Sex: M Population Size: 1 Sources: |
Other AEs: Coordination and balance disturbances... Other AEs: Coordination and balance disturbances (1 patient) Sources: |
12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy, 35 years n = 255 Health Status: unhealthy Condition: epilepsy Age Group: 35 years Sex: M+F Population Size: 255 Sources: |
Disc. AE: Dizziness, Somnolence... AEs leading to discontinuation/dose reduction: Dizziness Sources: Somnolence Vertigo Ataxia Blurred vision Dysarthria |
300 mg single, oral Overdose |
unhealthy, 54 years n = 1 Health Status: unhealthy Condition: refractory seizures Age Group: 54 years Sex: M Population Size: 1 Sources: |
Other AEs: Somnolence, Bradycardia... Other AEs: Somnolence (1 patient) Sources: Bradycardia (1 patient) Hyponatremia (1 patient) |
264 mg single, oral Overdose Dose: 264 mg Route: oral Route: single Dose: 264 mg Sources: |
unknown n = 1 Health Status: unknown Population Size: 1 Sources: |
Other AEs: Agitation, Aggressive behavior... Other AEs: Agitation (1 patient) Sources: Aggressive behavior (1 patient) |
12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: epilepsy Sources: |
Disc. AE: Hostility, Aggression... AEs leading to discontinuation/dose reduction: Hostility (20%) Sources: Aggression (20%) Irritability Anger Anxiety |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Ataxia | 1 patient | 10 mg single, oral Overdose |
healthy, 2 years n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 Sources: |
Drowsiness | 1 patient | 10 mg single, oral Overdose |
healthy, 2 years n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 Sources: |
Coordination and balance disturbances | 1 patient | 2 mg single, oral Overdose |
healthy, 2 years n = 1 Health Status: healthy Age Group: 2 years Sex: M Population Size: 1 Sources: |
Ataxia | Disc. AE | 12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy, 35 years n = 255 Health Status: unhealthy Condition: epilepsy Age Group: 35 years Sex: M+F Population Size: 255 Sources: |
Blurred vision | Disc. AE | 12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy, 35 years n = 255 Health Status: unhealthy Condition: epilepsy Age Group: 35 years Sex: M+F Population Size: 255 Sources: |
Dizziness | Disc. AE | 12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy, 35 years n = 255 Health Status: unhealthy Condition: epilepsy Age Group: 35 years Sex: M+F Population Size: 255 Sources: |
Dysarthria | Disc. AE | 12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy, 35 years n = 255 Health Status: unhealthy Condition: epilepsy Age Group: 35 years Sex: M+F Population Size: 255 Sources: |
Somnolence | Disc. AE | 12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy, 35 years n = 255 Health Status: unhealthy Condition: epilepsy Age Group: 35 years Sex: M+F Population Size: 255 Sources: |
Vertigo | Disc. AE | 12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy, 35 years n = 255 Health Status: unhealthy Condition: epilepsy Age Group: 35 years Sex: M+F Population Size: 255 Sources: |
Bradycardia | 1 patient | 300 mg single, oral Overdose |
unhealthy, 54 years n = 1 Health Status: unhealthy Condition: refractory seizures Age Group: 54 years Sex: M Population Size: 1 Sources: |
Hyponatremia | 1 patient | 300 mg single, oral Overdose |
unhealthy, 54 years n = 1 Health Status: unhealthy Condition: refractory seizures Age Group: 54 years Sex: M Population Size: 1 Sources: |
Somnolence | 1 patient | 300 mg single, oral Overdose |
unhealthy, 54 years n = 1 Health Status: unhealthy Condition: refractory seizures Age Group: 54 years Sex: M Population Size: 1 Sources: |
Aggressive behavior | 1 patient | 264 mg single, oral Overdose Dose: 264 mg Route: oral Route: single Dose: 264 mg Sources: |
unknown n = 1 Health Status: unknown Population Size: 1 Sources: |
Agitation | 1 patient | 264 mg single, oral Overdose Dose: 264 mg Route: oral Route: single Dose: 264 mg Sources: |
unknown n = 1 Health Status: unknown Population Size: 1 Sources: |
Aggression | 20% Disc. AE |
12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: epilepsy Sources: |
Hostility | 20% Disc. AE |
12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: epilepsy Sources: |
Anger | Disc. AE | 12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: epilepsy Sources: |
Anxiety | Disc. AE | 12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: epilepsy Sources: |
Irritability | Disc. AE | 12 mg 1 times / day steady, oral Recommended Dose: 12 mg, 1 times / day Route: oral Route: steady Dose: 12 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: epilepsy Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000PharmR.pdf#page=6 Page: 6.0 |
Sample Use Guides
Starting dose is 2 mg once daily at bedtime. May increase dose based on clinical response and tolerability by increments of 2 mg once daily no more frequently than at weekly intervals. Recommended maintenance dose is for Partial-Onset Seizures – 8 to 12 mg once daily at bedtime; for Primary Generalized Tonic-Clonic Seizures – 8 mg once daily at bedtime. Individual dosing should be adjusted based on clinical response and tolerability.
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/26306919
in vitro ischemia model in murine brain endothelial cells
Substance Class |
Chemical
Created
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admin
on
Edited
Fri Dec 15 15:56:39 GMT 2023
by
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on
Fri Dec 15 15:56:39 GMT 2023
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Record UNII |
H821664NPK
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Record Status |
Validated (UNII)
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Record Version |
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EMA ASSESSMENT REPORTS |
FYCOMPA (AUTHORIZED: EPILEPSIES, PARTIAL)
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WHO-ATC |
N03AX22
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WHO-VATC |
QN03AX22
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DEA NO. |
2261
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NCI_THESAURUS |
C47795
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FDA ORPHAN DRUG |
380912
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LIVERTOX |
NBK548508
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NDF-RT |
N0000186106
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H821664NPK
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H821664NPK
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8834
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380917-97-5
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DB08883
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71015
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100000124527
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CHEMBL1214124
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9924495
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C75029
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SUB32160
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1356552
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71013
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Perampanel
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m11706
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PERAMPANEL
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N0000020016
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PRIMARY | AMPA Receptor Antagonists [MoA] | ||
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C551441
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SS-46
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Related Record | Type | Details | ||
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TARGET->NEGATIVE ALLOSTERIC MODULATOR (NAM) |
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METABOLIC ENZYME -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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BINDER->LIGAND |
BINDING
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TRANSPORTER -> INHIBITOR |
Thus, the unbound Cmax is about 0.09 μM, much lower than 8.5 μM. Therefore, E2007 is unlikely to inhibit OAT1, OAT3, OCT1 and OCT3 in vivo.
Ki
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TRANSPORTER -> INHIBITOR |
Thus, the unbound Cmax is about 0.09 μM, much lower than 8.5 μM. Therefore, E2007 is unlikely to inhibit OAT1, OAT3, OCT1 and OCT3 in vivo.
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TRANSPORTER -> INHIBITOR |
Thus, the unbound Cmax is about 0.09 μM, much lower than 8.5 μM. Therefore, E2007 is unlikely to inhibit OAT1, OAT3, OCT1 and OCT3 in vivo.
Ki
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SALT/SOLVATE -> PARENT | |||
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TARGET -> INHIBITOR | |||
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SOLVATE->ANHYDROUS | |||
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TRANSPORTER -> INHIBITOR |
Thus, the unbound Cmax is about 0.09 μM, much lower than 8.5 μM. Therefore, E2007 is unlikely to inhibit OAT1, OAT3, OCT1 and OCT3 in vivo.
Ki
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EXCRETED UNCHANGED |
URINE
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Related Record | Type | Details | ||
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METABOLITE INACTIVE -> PARENT |
In vitro studies show that the primary oxidative metabolic route of perampanel is via cytochrome P450 (CYP)3A4 and/or CYP3A5, based on the results of metabolism by recombinant human CYPs, and inhibition studies using anti-CYP3A4 and ketoconazole in human liver microsomes.
FECAL; URINE
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METABOLITE -> PARENT | |||
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METABOLITE INACTIVE -> PARENT |
URINE
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METABOLITE INACTIVE -> PARENT |
URINE
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METABOLITE INACTIVE -> PARENT |
In vitro studies show that the primary oxidative metabolic route of perampanel is via cytochrome P450 (CYP)3A4 and/or CYP3A5, based on the results of metabolism by recombinant human CYPs, and inhibition studies using anti-CYP3A4 and ketoconazole in human liver microsomes.
FECAL; URINE
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METABOLITE -> PARENT | |||
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METABOLITE INACTIVE -> PARENT |
FECAL; URINE
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METABOLITE -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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Tmax | PHARMACOKINETIC |
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HIGH-FAT MEAL |
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