PERAMPANEL HYDRATE (4:3)

Details

Stereochemistry	ACHIRAL
Molecular Formula	4C23H15N3O.3H2O
Molecular Weight	1451.5846
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.O.O=C1N(C=C(C=C1C2=CC=CC=C2C#N)C3=CC=CC=N3)C4=CC=CC=C4.O=C5N(C=C(C=C5C6=CC=CC=C6C#N)C7=CC=CC=N7)C8=CC=CC=C8.O=C9N(C=C(C=C9C%10=CC=CC=C%10C#N)C%11=CC=CC=N%11)C%12=CC=CC=C%12.O=C%13N(C=C(C=C%13C%14=CC=CC=C%14C#N)C%15=CC=CC=N%15)C%16=CC=CC=C%16

InChI

InChIKey=PDWMJDKMSASBNE-UHFFFAOYSA-N

InChI=1S/4C23H15N3O.3H2O/c4*24-15-17-8-4-5-11-20(17)21-14-18(22-12-6-7-13-25-22)16-26(23(21)27)19-9-2-1-3-10-19;;;/h4*1-14,16H;3*1H2

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202834s005lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate receptor ionotropic AMPA 41 Target ID: CHEMBL2096670 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202834s005lbl.pdf	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Epilepsy 121 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202834s005lbl.pdf	Primary		Approved 8429	FYCOMPA Approved Use Indicated 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 Date 2012

C_max

Value	Dose	Co-administered	Analyte	Population
371.9 μg/L REVIEW https://pubmed.ncbi.nlm.nih.gov/25495693/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/25495693/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/25495693/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/25495693/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
98.1 h REVIEW https://pubmed.ncbi.nlm.nih.gov/25495693/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/25495693/	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
4.5% REVIEW https://pubmed.ncbi.nlm.nih.gov/25495693/	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 Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/32349889	healthy, 2 years n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/32349889	Other AEs: Drowsiness, Ataxia... Other AEs: Drowsiness (1 patient) Ataxia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/32349889
2 mg single, oral Overdose Dose: 2 mg Route: oral Route: single Dose: 2 mg Sources: https://pubmed.ncbi.nlm.nih.gov/32349889	healthy, 2 years n = 1 Health Status: healthy Age Group: 2 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/32349889	Other AEs: Coordination and balance disturbances... Other AEs: Coordination and balance disturbances (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/32349889
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202834lbl.pdf	unhealthy, 35 years n = 255 Health Status: unhealthy Condition: epilepsy Age Group: 35 years Sex: M+F Population Size: 255 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202834lbl.pdf	Disc. AE: Dizziness, Somnolence... AEs leading to discontinuation/dose reduction: Dizziness Somnolence Vertigo Ataxia Blurred vision Dysarthria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202834lbl.pdf
300 mg single, oral Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://pubmed.ncbi.nlm.nih.gov/29299938	unhealthy, 54 years n = 1 Health Status: unhealthy Condition: refractory seizures Age Group: 54 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/29299938	Other AEs: Somnolence, Bradycardia... Other AEs: Somnolence (1 patient) Bradycardia (1 patient) Hyponatremia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/29299938
264 mg single, oral Overdose Dose: 264 mg Route: oral Route: single Dose: 264 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202834lbl.pdf	unknown n = 1 Health Status: unknown Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202834lbl.pdf	Other AEs: Agitation, Aggressive behavior... Other AEs: Agitation (1 patient) Aggressive behavior (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202834lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202834lbl.pdf	unhealthy Health Status: unhealthy Condition: epilepsy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202834lbl.pdf	Disc. AE: Hostility, Aggression... AEs leading to discontinuation/dose reduction: Hostility (20%) Aggression (20%) Irritability Anger Anxiety Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202834lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781	inhibitor 1767	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 UGT1A1 204 UGT1A4 77 UGT1A6 108 CYP2C8 911 UGT1A9 116 UGT2B7 146 P-gp 1461 BCRP 699 OAT1 599 OAT3 642 OCT1 512 OCT3 150	P-gp 1537 BCRP 561 OATP1B1 406 OATP1B3 350 OAT1 326 OAT2 115 OAT3 339 OAT4 78 OCT1 327 OCT2 355 OCT3 80 CYP3A4/5 85 CYP1A2 1054 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667	CYP1A2 701 CYP2B6 547 UGT1A1 69 UGT1A4 8

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
UGT1A1 254	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	likely
UGT1A4 80	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	likely
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
UGT1A4 80	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
UGT1A6 141	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	weak [IC50 >30 uM]
UGT1A9 121	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164;18	weak [Inhibition 30 uM]
UGT2B7 157	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164;18	weak [Inhibition 30 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	weak
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	weak
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	weak
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	weak
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	weak
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	weak
OCT3 150	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	weak
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	weak
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164;193	yes [Ki 40.6 uM]	weak (co-administration study) Comment: time-dependent inhibition;decreased AUC0-inf and Cmax of midazolam (a CYP3A4 substrate) by 13% and 15%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164;193
CYP2B6 1001	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=192 Page: 192.0	yes
OAT2 147	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=192 Page: 192.0	likely
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=192 Page: 192.0	likely
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=192 Page: 192.0	likely
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=192 Page: 192.0	likely
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=192 Page: 192.0	likely
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=192 Page: 192.0	likely
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
OAT2 115	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
OAT4 78	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
OCT3 80	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	no
CYP3A4/5 85	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164;192	yes	weak (co-administration study) Comment: Co-administration with ketoconazole (a strong inhibitor of CYP3A4) increased perampanel AUC by 20%; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000ClinPharmR.pdf#page=164 Page: 164;192

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202834Orig1s000PharmR.pdf#page=6 Page: 6.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:71013	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:71013
ChemicalBook	CB12598797	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB12598797
MolPort	MolPort-035-395-270	https://www.molport.com/shop/molecule-link/MolPort-035-395-270
ZINC	ZINC000030691797	http://zinc15.docking.org/substances/ZINC000030691797

PubMed

Title	Date	PubMed
Safety and efficacy of perampanel in advanced Parkinson's disease: a randomized, placebo-controlled study.	2010 May 15	20461807

Patents

Sample Use Guides

In Vivo Use Guide

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

in vitro ischemia model in murine brain endothelial cells

Substance Class	Chemical Created by `admin` on `Sat Dec 16 07:50:54 GMT 2023` Edited by `admin` on `Sat Dec 16 07:50:54 GMT 2023`
Record UNII	8LIX22217M
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PERAMPANEL HYDRATE (4:3)

Common Name

English

PERAMPANEL HYDRATE [JAN]

Common Name

English

Code System Code Type Description

CAS

1571982-04-1