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			{{Short description|Anti-epileptic medication}}
	{{drugbox | Verifiedfields = changed
			{{Use dmy dates|date=March 2024}}
	| verifiedrevid = 403075672
			{{Infobox drug
	|
			| Verifiedfields = changed
	| IUPAC_name = 5'-(2-cyanophenyl)-1'-phenyl-2,3'-bipyridinyl-6'(1'H)-one
			| Watchedfields = changed
	| image = Perampanel.png
			| verifiedrevid = 408536313
	| width = 240
			| image = Perampanel structure.svg
	| CAS_number = 380917-97-5
			| alt = Skeletal formula of perampanel
	| synonyms =
			| width = 200
	| ATC_prefix = none
	| ATC_suffix =		| caption =
			| image2 = Perampanel molecule ball.png
	| PubChem = 9924495
			| alt2 = Ball-and-stick model of the perampanel molecule
	| DrugBank =
	| KEGG_Ref = {{keggcite|changed|kegg}}
			<!-- Clinical data -->
			| pronounce =
			| tradename = Fycompa
			| Drugs.com = {{drugs.com|monograph|perampanel}}
			| MedlinePlus = a614006
			| DailyMedID = Perampanel
			| pregnancy_AU = B3
			| pregnancy_AU_comment =
			| pregnancy_category =
			| routes_of_administration = ]
			| class = ]
			| ATC_prefix = N03
			| ATC_suffix = AX22
			| ATC_supplemental =
			<!-- Legal status -->
			| legal_AU = S4
			| legal_AU_comment = <ref name="AusPAR: Perampanel hemisesquihydrate">{{cite web | title=AusPAR: Perampanel hemisesquihydrate | website=Therapeutic Goods Administration (TGA) | date=10 May 2021 | url=https://www.tga.gov.au/auspar/auspar-perampanel-hemisesquihydrate-0 | access-date=12 June 2021}}</ref><ref>{{Cite web|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2014-PI-02011-1|title = TGA eBS - Product and Consumer Medicine Information Licence}}</ref><ref>{{cite web | title=Fycompa | website=NPS MedicineWise | date=15 July 2021 | url=https://www.nps.org.au/medicine-finder/fycompa-tablets#full-pi | access-date=19 February 2022}}</ref><ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2014 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/resource/guidance/prescription-medicines-registration-new-chemical-entities-australia-2014 | access-date=10 April 2023}}</ref>
			| legal_BR = B1
			| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=] |language=pt-BR |publication-date=4 April 2023}}</ref>
			| legal_CA = Rx-only
			| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=Health Canada | date=February 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=24 March 2024}}</ref>
			| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
			| legal_DE_comment =
			| legal_NZ = <!-- Class A, B, C -->
			| legal_NZ_comment =
			| legal_UK = POM
			| legal_UK_comment =
			| legal_US = Schedule III
			| legal_US_comment = <ref name="Fycompa FDA label" />
			| legal_EU = Rx-only
			| legal_EU_comment =
			| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
			| legal_UN_comment =
			| legal_status = <!-- For countries not listed above -->
			<!-- Pharmacokinetic data -->
			| bioavailability = 116%<ref>{{cite journal| vauthors = Yang X, Wu TC, Yuxin MA, Lee JY, Bhattaram VA, Mehta MU |title=U.S. FDA Clinical Pharmacology Review. Fycompa (perampanel)|page=25|url=https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM332052.pdf}}</ref>
			| protein_bound = 95–96%
			| metabolism = ], mostly via ] and/or ]
			| metabolites =
			| onset =
			| elimination_half-life = 105 hours, 295 hours (moderate hepatic impairment)
			| duration_of_action =
			| excretion = 70% faeces, 30% urine
			<!-- Identifiers -->
			| index2_label = as hydrate
			| CAS_number_Ref = {{cascite|correct|??}}
			| CAS_number = 380917-97-5
			| CAS_number2 = 1571982-04-1
			| CAS_supplemental =
			| PubChem = 9924495
			| PubChem2 = 70679123
			| IUPHAR_ligand = 7050
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank = DB08883
			| DrugBank2 = DBSALT001824
			| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
			| ChemSpiderID = 8100130
			| ChemSpiderID2 = 28533413
			| UNII_Ref = {{fdacite|changed|FDA}}
			| UNII = H821664NPK
			| UNII2 = 8LIX22217M
			| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D08964		| KEGG = D08964
			| KEGG2 = D10780
	| C = 23 | H = 15 | N = 3 | O = 1
			| ChEBI_Ref = {{ebicite|changed|EBI}}
	| molecular_weight = 349.384 g/mol
			| ChEBI = 71013
	| smiles = N#Cc2ccccc2-c1cc(-c4ncccc4)cn(c1=O)-c3ccccc3
			| ChEBI2 = 71015
	| bioavailability =
			| ChEMBL_Ref = {{ebicite|changed|EBI}}
	| protein_bound =
			| ChEMBL = 1214124
	| metabolism =
			| NIAID_ChemDB =
	| elimination_half-life =
			| PDB_ligand = 6ZP
	| excretion =
			| synonyms = E2007
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
	| pregnancy_US = <!-- A / B / C / D / X -->
			<!-- Chemical and physical data -->
	| pregnancy_category=
			| IUPAC_name = 5'-(2-cyanophenyl)-1'-phenyl-2,3'-bipyridinyl-6'(1''H'')-one
	| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
			| C=23 | H=15 | N=3 | O=1
	| legal_CA = <!-- Schedule I -->
			| SMILES = N#Cc2ccccc2-c1cc(-c4ncccc4)cn(c1=O)-c3ccccc3
	| legal_UK = <!-- Class A -->
			| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
	| legal_US =
			| StdInChI = 1S/C23H15N3O/c24-15-17-8-4-5-11-20(17)21-14-18(22-12-6-7-13-25-22)
	| legal_status = Investigational New Medicine
			16-26(23(21)27)19-9-2-1-3-10-19/h1-14,16H
	| routes_of_administration =
			| StdInChI2 = 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
			| StdInChI_comment =
			| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChIKey = PRMWGUBFXWROHD-UHFFFAOYSA-N
			| StdInChIKey2 = PDWMJDKMSASBNE-UHFFFAOYSA-N
			| density =
			| density_notes =
			| melting_point =
			| melting_high =
			| melting_notes =
			| boiling_point =
			| boiling_notes =
			| solubility =
			| sol_units =
			| specific_rotation =
	}}		}}
			'''Perampanel''', sold under the brand name '''Fycompa''', is an ] developed by ] that is used in addition to other drugs to treat ] and generalized ] for people older than twelve years.<ref name="Fycompa FDA label">{{cite web | title=Fycompa- perampanel tablet Fycompa- perampanel suspension | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=71cf3309-e182-473c-8b0b-280cabd0e122 | access-date=12 June 2021}}</ref> It was first approved in 2012, and {{as of|2016|lc=yes}}, its optimal role in the treatment of epilepsy relative to other drugs was not clear.<ref name=Besag2016rev>{{cite journal | vauthors = Besag FM, Patsalos PN | title = Clinical efficacy of perampanel for partial-onset and primary generalized tonic-clonic seizures | journal = Neuropsychiatric Disease and Treatment | volume = 12 | pages = 1215–20 | date = 2016 | pmid = 27274257 | pmc = 4876101 | doi = 10.2147/NDT.S83842 | s2cid = 14176469 | doi-access = free }}</ref> It was the first antiepileptic drug in the class of selective ] of ]s.<ref name=Chong2016rev>{{cite journal | vauthors = Chong DJ, Lerman AM | title = Practice Update: Review of Anticonvulsant Therapy | journal = Current Neurology and Neuroscience Reports | volume = 16 | issue = 4 | pages = 39 | date = April 2016 | pmid = 26984292 | doi = 10.1007/s11910-016-0640-y | s2cid = 9090302 }}</ref>
	'''Perampanel''' is a drug developed by Eisai Co., which acts as a selective antagonist for the ] subtype of ionotropic ]s. It is being researched for several possible clinical applications including the treatment of ].<ref name="Gottwald2008">{{cite journal |author=Gottwald MD, Aminoff MJ |title=New frontiers in the pharmacological management of Parkinson's disease |journal=Drugs Today |volume=44 |issue=7 |pages=531–45 |year=2008 |month=July |pmid=18806903 |doi=10.1358/dot.2008.44.7.1217105 |url=}}</ref>
			<!-- Side effects -->
			The drug label has a ] that the drug may cause serious psychiatric and behavioral changes; it may cause homicidal or suicidal thoughts.<ref name="Fycompa FDA label"/> Other side effects have included dizziness, somnolence, vertigo, aggression, anger, ], blurred vision, irritability, and ].<ref name="Fycompa FDA label"/> Perampanel reduced the effectiveness of levonorgestrel ] by about 40%.<ref name="Fycompa FDA label"/> Women who may get pregnant should not take it as studies in animals show it may harm a fetus.<ref name=EMAreport>EMA {{Webarchive|url=https://web.archive.org/web/20180920084321/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002434/WC500130815.pdf |date=20 September 2018 }}. {{cite web| url =http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002434/human_med_001572.jsp&mid=WC0b01ac058001d124| title =Index pagel| date =17 September 2018| access-date =21 August 2012| archive-date =20 June 2018| archive-url =https://web.archive.org/web/20180620155355/http://www.ema.europa.eu/ema//index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002434%2Fhuman_med_001572.jsp&mid=WC0b01ac058001d124| url-status =dead}}</ref> Perampanel is liable to be abused; very high doses produced euphoria responses similar to ].<ref name="Fycompa FDA label"/> It is designated as a Schedule III ] by the ].<ref name="Fycompa FDA label"/>
			As of August 2016 perampanel had been studied and development discontinued in migraine, multiple sclerosis, neuropathic pain, and Parkinson's disease.<ref name=AdisInsight>{{cite web|title=Perampanel|url=http://adisinsight.springer.com/drugs/800015670|publisher=AdisInsight|access-date=29 August 2016}}</ref>
			==Medical uses==
			Perampanel is used in addition to other drugs to treat ] and generalized ] for people older than twelve years.<ref name="Fycompa FDA label"/>
			A 2016 review found it effective for both indications but due to the newness of the drug was unable to describe its optimal role in the treatment of epilepsy relative to other drugs.<ref name=Besag2016rev/> A 2014 review of the probability of added benefit of perampanel to the standard of care was unable to come to any conclusions, as no trial conducted by Eisai compared perampanel to a drug within the standard of care, but only to placebo.<ref>{{cite journal | title = Perampanel -- Benefit Assessment According to §35a Social Code Book V . | journal = Extract of Dossier Assessment No. A14-16. IQWiG Dossier Assessment Extracts. | date = 13 August 2014 | pmid = 26677496 | url = https://www.iqwig.de/download/A14-16_Perampanel_Extract-of-dossier-assessment.pdf | author1 = Institute for Quality Efficiency in Health Care }}</ref>
			==Contraindications==
			Based on animal data, perampanel may cause fetal harm;<ref name="Fycompa FDA label"/> it is not recommended for women of child-bearing age not taking contraception.<ref name=EMAreport/>
			People with severe liver impairment or severe kidney disease, including those on dialysis, should not take perampanel.<ref name="Fycompa FDA label"/>
			==Side effects==
			Perampanel's label has a ] noting that some people taking the drug have undergone serious psychiatric and behavioral changes. These events occurred in people who had no history of such issues, as well as people who had such a history. The psychiatric changes included mood changes like euphoric mood, anger, irritability, aggression, belligerence, agitation, and anxiety, as well as psychosis (acute psychosis, hallucinations, delusions, paranoia) and delirium (delirium, confusional state, disorientation, memory impairment). Behavioral changes included physical assault and homicidal ideation and/or threats.<ref name="Fycompa FDA label"/>
			Other serious side effects include suicidal thoughts or behavior (like all anti-epileptic drugs), dizziness and gait disturbance, somnolence and fatigue, risk of falls, and increased risk of seizures if the drug is quickly withdrawn.<ref name="Fycompa FDA label"/>
			In clinical trials, dizziness, somnolence, vertigo, aggression, anger, ], blurred vision, irritability, and ] were the side effects that most commonly led people to leave the trial.<ref name="Fycompa FDA label"/>
			Perampanel is liable to be abused: very high doses produced euphoria responses and dissociative effects similar to ], although subjects liked it less and had experienced it more negatively than ketamine.<ref name="Fycompa FDA label"/> It is designated as a Schedule III ] by the ].<ref name="Fycompa FDA label"/> A study of ] in rats found withdrawal symptoms when the drug was removed; dependence in humans wasn't studied well enough to make generalizations as of April 2016.<ref name="Fycompa FDA label"/> There is limited experience with overdose.<ref name="Fycompa FDA label"/>
			== Interactions ==
			Perampanel reduced the effectiveness of levonorgestrel ] by about 40%. Other antieptilectic drugs that induce cytochrome P450, including ], ], and ] decrease the effectiveness of perampanel by 50-67%. Use of perampanel with strong CYP3A inducers like ] or ] is not recommended. Use of perampanel with CNS depressants like alcohol may increase the effect of the CNS depressant.<ref name="Fycompa FDA label"/>
			==Pharmacology==
			{{Technical|date=November 2023|section}}
			Perampanel is a selective ] of ]s, the major subtype of ]s.<ref>{{cite journal | vauthors = Rogawski MA | title = Revisiting AMPA receptors as an antiepileptic drug target | journal = Epilepsy Currents | volume = 11 | issue = 2 | pages = 56–63 | date = March 2011 | pmid = 21686307 | pmc = 3117497 | doi = 10.5698/1535-7511-11.2.56 | s2cid = 15246804 }}</ref><ref name=Hanada2013rev>{{cite journal | vauthors = Rogawski MA, Hanada T | title = Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist | journal = Acta Neurologica Scandinavica. Supplementum | volume = 127 | issue = 197 | pages = 19–24 | date = 2013 | pmid = 23480152 | pmc = 4506647 | doi = 10.1111/ane.12100 }}</ref> It was the first drug of this class approved for epilepsy.<ref name=Chong2016rev/>
			Whole-cell voltage clamp studies have demonstrated that perampanel is a negative allosteric AMPA receptor antagonist.<ref name="Chao2014">{{cite journal | vauthors = Chen CY, Matt L, Hell JW, Rogawski MA | title = Perampanel inhibition of AMPA receptor currents in cultured hippocampal neurons | journal = PLOS ONE | volume = 9 | issue = 9 | pages = e108021 | date = 17 September 2014 | pmid = 25229608 | pmc = 4168215 | doi = 10.1371/journal.pone.0108021 | bibcode = 2014PLoSO...9j8021C | s2cid = 7519077 | doi-access = free }}</ref> Perampanel caused a slow (τ~1&nbsp;s at 3&nbsp;μM), concentration-dependent inhibition of AMPA receptor currents. The rates of block and unblock of AMPA receptor currents were 1.5×10<sup>5</sup>&nbsp;M<sup>−1</sup>&nbsp;s<sup>−1</sup> and 0.58&nbsp;s<sup>−1</sup>, respectively. Perampanel did not affect NMDA receptor currents. The extent of block (IC<sub>50</sub>, 0.56&nbsp;μM) was similar at all agonist concentrations, demonstrating a noncompetitive blocking action. Parampanel did affect AMPA receptor desensitization, or the ratio of peak to late response to rapid application of AMPA.<ref name="Chao2014"/> Perampanel is a selective negative allosteric AMPA receptor antagonist of high-affinity and slow blocking kinetics, and is not use-dependent.
			Perampanel has a prolonged terminal half-life in humans of approximately 105 hours. The drug is 95% bound to plasma protein. Its primary route of metabolism is by ]. It does not induce ] enzymes. About 70% of the dose is excreted in the feces and 30% in the urine; less than 2% of the dose is excreted unchanged into the urine.<ref name=EMAreport/>
			==Chemistry==
			Perampanel's chemical formula is 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile; it has a ] core structure that sets it apart from other ] antagonists.<ref name=Hanada2013rev/>
			The tablets contain lactose monohydrate, low substituted hydroxypropyl cellulose, povidone, microcrystalline cellulose, magnesium stearate, hypromellose, polyethylene glycol, talc, and titanium dioxide in addition to the API; the oral suspension contains sorbitol, microcrystalline cellulose, carboxymethylcellulose sodium, poloxamer, simethicone, citric acid, sodium benzoate and purified water in addition to the API.<ref name="Fycompa FDA label"/>
			==History==
			It was approved for marketing under the brand name Fycompa by the ] (EMA) in July 2012,<ref name=EMAreport/> and as of July 2016, was approved as an adjunct treatment of partial-onset seizures with or without secondarily generalised seizures in people with epilepsy older than twelve years and as an adjunct treatment of primary generalised tonic-clonic seizures for people older than twelve years who have idiopathic generalised epilepsy.<ref name=EMAreport/>
			It was first approved by the FDA under the same brand name in October 2012, and then in June 2015, for the same uses as those in the European Union; it was one of four new drugs for epilepsy approved between 2010 and 2016, along with ] (Onfi), ] (Potiga), and ] (Aptiom).<ref name=Chong2016rev/>
	==References==		==Research==
			As of August 2016, perampanel had been studied and development discontinued in migraine, multiple sclerosis, neuropathic pain, and Parkinson's disease.<ref name=AdisInsight/>
	{{reflist}}
			== References ==
	{{Glutamate_receptor_ligands}}
			{{Reflist}}
	{{pharma-stub}}		{{Anticonvulsants}}
			{{Ionotropic glutamate receptor modulators}}
			{{Portal bar | Medicine}}
	]		]
			]
			]
	]		]
	]		]
	]		]