Details of the Drug

General Information of Drug (ID: DMJDYNQ)

• Drug Name: E-2007
• Synonyms: Perampanel; E 2007; Perampanel (USAN); 2-(2-oxo-1-phenyl-5-pyridin-2-yl-pyridin-3-yl)benzonitrile; 3-(2-Cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one

Indication

Disease Entry	ICD 11	Status	REF
Diabetic neuropathy	8C0Z	Approved	[1]
Parkinson disease	8A00.0	Discontinued in Phase 3	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 349.4
  Logarithm of the Partition Coefficient (xlogp); 3.4
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  Absorption: The drug is rapidly and completely absorbed following oral administration []
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 0.1 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 105 hours [3]
  Metabolism: The drug is metabolized via the CYP3A4 and/or CYP3A5 primary oxidation and by sequential glucuronidation []
  Unbound Fraction: The unbound fraction of drug in plasma is 0.05% [3]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.36 L/kg [3]
• Chemical Identifiers:
  Formula: C23H15N3O
  IUPAC Name: 2-(2-oxo-1-phenyl-5-pyridin-2-ylpyridin-3-yl)benzonitrile
  Canonical SMILES: C1=CC=C(C=C1)N2C=C(C=C(C2=O)C3=CC=CC=C3C#N)C4=CC=CC=N4
  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
  InChIKey: PRMWGUBFXWROHD-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 9924495
  ChEBI ID: CHEBI:71013
  CAS Number: 380917-97-5
  DrugBank ID: DB08883
  TTD ID: D0U3ED
  INTEDE ID: DR1256
  ACDINA ID: D00519
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glutamate receptor AMPA (GRIA)	TTAN6JD	NOUNIPROTAC	Modulator	[4]
Glutamate receptor AMPA 1 (GRIA1)	TTVPQTF	GRIA1_HUMAN	Inhibitor	[5]
Glutamate receptor AMPA 2 (GRIA2)	TT9HLZ0	GRIA2_HUMAN	Inhibitor	[5]
Glutamate receptor AMPA 3 (GRIA3)	TT82EZV	GRIA3_HUMAN	Inhibitor	[5]
Glutamate receptor AMPA 4 (GRIA4)	TTPJR0G	GRIA4_HUMAN	Inhibitor	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[7]
Cytochrome P450 3A5 (CYP3A5) Main DME	DEIBDNY	CP3A5_HUMAN	Substrate	[8]

Molecular Expression Atlas of This Drug

• The Studied Disease: Diabetic neuropathy
• ICD Disease Classification: 8C0Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Glutamate receptor AMPA 1 (GRIA1)	DTT	GRIA1	1.46E-06	-0.63	-0.78
Glutamate receptor AMPA (GRIA)	DTT	NO-GeName	1.79E-04	-0.69	-0.58
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	7.36E-01	1.62E-02	1.08E-01
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	9.96E-01	-3.17E-03	-1.84E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from E-2007 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of E-2007 caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of E-2007 caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[9]
Levomilnacipran	DMV26S8	Moderate	Antagonize the effect of E-2007 when combined with Levomilnacipran.	Chronic pain [MG30]	[10]
Vortioxetine	DM6F1PU	Moderate	Antagonize the effect of E-2007 when combined with Vortioxetine.	Depression [6A70-6A7Z]	[10]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of E-2007 and Esketamine.	Depression [6A70-6A7Z]	[11]
Oestradiol valerate and dienogest	DMZK0FQ	Moderate	Increased metabolism of E-2007 caused by Oestradiol valerate and dienogest mediated induction of CYP450 enzyme.	Endometriosis [GA10]	[9]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of E-2007 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[9]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of E-2007 and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[12]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of E-2007 and Lasmiditan.	Migraine [8A80]	[13]
Elagolix	DMB2C0E	Moderate	Increased metabolism of E-2007 caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[9]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
FD&C blue no. 2	E00446	2723854	Colorant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Perampanel 10 mg tablet	10 mg	Oral Tablet	Oral
Perampanel 12 mg tablet	12 mg	Oral Tablet	Oral
Perampanel 2 mg tablet	2 mg	Oral Tablet	Oral
Perampanel 8 mg tablet	8 mg	Oral Tablet	Oral
Perampanel 4 mg tablet	4 mg	Oral Tablet	Oral
Perampanel 6 mg tablet	6 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7050).
• [2] BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [5] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [6] The clinical pharmacology profile of the new antiepileptic drug perampanel: A novel noncompetitive AMPA receptor antagonist. Epilepsia. 2015 Jan;56(1):12-27.
• [7] Perampanel (Fycompa): a review of clinical efficacy and safety in epilepsy. P T. 2016 Nov;41(11):683-698.
• [8] FDA label of Perampanel. The 2020 official website of the U.S. Food and Drug Administration.
• [9] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [10] Belcastro V, Costa C, Striano P "Levetiracetam-associated hyponatremia." Seizure 17 (2008): 389-90. [PMID: 18584781]
• [11] Cerner Multum, Inc. "Australian Product Information.".
• [12] Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
• [13] Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.