4-Aminopyridine

{{cs1 config|name-list-style=vanc|display-authors=6}} {{chembox | Watchedfields = changed | verifiedrevid = 477221003 | ImageFile_Ref = {{chemboximage|correct|??}} | ImageFile = 4-aminopyridine.svg | ImageClass = skin-invert-image | ImageSize = 80px | ImageFileL1 = 4-aminopyridine-from-xtal-3D-bs-17.png | ImageClassL1 = bg-transparent | ImageFileR1 = 4-aminopyridine-from-xtal-3D-sf.png | ImageClassR1 = bg-transparent | ImageFile2 = 4-aminopyridine_sample.jpg | ImageSize2 = 220px | PIN = Pyridin-4-amine | OtherNames = 4-Pyridinamine 4-Pyridylamine Para-aminopyridine fampridine (INN) dalfampridine (USAN) | Section1 = {{Chembox Identifiers | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 1664 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = BH3B64OKL9 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D04127 | KEGG2_Ref = {{keggcite|correct|kegg}} | KEGG2 = C13728 | InChI = 1/C5H6N2/c6-5-1-3-7-4-2-5/h1-4H,(H2,6,7) | InChIKey = NUKYPUAOHBNCPY-UHFFFAOYAH | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C5H6N2/c6-5-1-3-7-4-2-5/h1-4H,(H2,6,7) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = NUKYPUAOHBNCPY-UHFFFAOYSA-N | CASNo_Ref = {{cascite|correct|CAS}} | CASNo=504-24-5 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 284348 | DrugBank = DB06637 | EINECS = 207-987-9 | PubChem=1727 | IUPHAR_ligand = 2416 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 34385 | SMILES = n1ccc(N)cc1 | MeSHName=4-Aminopyridine }} | Section2 = {{Chembox Properties | Formula=C5H6N2 | MolarMass=94.1146 g/mol | Appearance=colourless solid | Density= | MeltingPtC = 155 to 158 | MeltingPt_notes = | BoilingPtC=273 | Solubility= polar organic solvents | pKb=4.83<ref>{{cite journal | vauthors = Albert A, Goldacre R, Phillips J | title = 455. The strength of heterocyclic bases | journal = Journal of the Chemical Society (Resumed) | pages = 2240–2249 | year = 1948 | doi = 10.1039/JR9480002240 }}</ref> }} | Section7 = {{Chembox Hazards | MainHazards= | FlashPt= | AutoignitionPt = }} | Section6 = {{Chembox Pharmacology | ATCCode_prefix = N07 | ATCCode_suffix = XX07 | AdminRoutes = Oral | Bioavail = 96% | Metabolism = | HalfLife = | ProteinBound = | Excretion = | Licence_EU= | INN=Fampridine | Legal_status = | Legal_US = Rx-only | Legal_US_comment = <ref>{{cite web | title = Ampyra- dalfampridine tablet, film coated, extended release | date = 20 December 2019 | website = DailyMed | url = https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=550eb76a-e4a6-4fa1-ad65-c0fd8b0ce783 | access-date = 24 August 2020 }}</ref> | Legal_UK = POM | Legal_UK_comment = <ref>{{cite web | title = Fampyra 10 mg prolonged-release tablets - Summary of Product Characteristics (SmPC) | date = 15 August 2018 | website = (emc) | url = https://www.medicines.org.uk/emc/product/4763/smpc | access-date = 24 August 2020 }}</ref> | Legal_AU = S4 | Legal_AU_comment = <ref>{{cite web | title = Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | date = 21 June 2022 | website = Therapeutic Goods Administration (TGA) | url = https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date = 30 March 2024 }}</ref> | Legal_CA = | Legal_CA_comment = | Legal_EU = Rx-only | Legal_EU_comment = <ref name="Fampyra EPAR" /> | Pregnancy_category = | Pregnancy_AU = C | Pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title = Dalfampridine (Ampyra) Use During Pregnancy | date = 22 June 2020 | website = Drugs.com | url = https://www.drugs.com/pregnancy/dalfampridine.html | access-date = 24 August 2020 }}</ref> }} }} thumb|right|240px|4-Aminopyridine '''4-Aminopyridine''' ('''4-AP''')<ref>{{Cite encyclopedia | vauthors = Lawrence E | title = 4-AP | pages = 1 | encyclopedia = Henderson's Dictionary of Biological Terms | edition = 10th | isbn = 978-0-470-21446-6 }}</ref> is an organic compound with the chemical formula {{chem2|H2NC5H4N}}. It is one of the three isomeric aminopyridines. It is used as a research tool in characterizing subtypes of the potassium channel. It has also been used as a drug, to manage some of the symptoms of multiple sclerosis,<ref>{{cite journal | vauthors = Solari A, Uitdehaag B, Giuliani G, Pucci E, Taus C | veditors = Solari A | title = Aminopyridines for symptomatic treatment in multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 2010 | issue = 4 | year = 2002 | pmid = 12804404 | pmc = 7047571 | doi = 10.1002/14651858.CD001330 | article-number = CD001330 }}</ref><ref>{{cite journal | vauthors = Korenke AR, Rivey MP, Allington DR | title = Sustained-release fampridine for symptomatic treatment of multiple sclerosis | journal = The Annals of Pharmacotherapy | volume = 42 | issue = 10 | pages = 1458–1465 | date = October 2008 | pmid = 18780812 | doi = 10.1345/aph.1L028 | s2cid = 207263182 }}</ref> and is indicated for symptomatic improvement of walking in adults with several variations of the disease.<ref name="austpre">{{cite journal | title = New Drugs: Fampridine | journal = Australian Prescriber | issue = 34 | pages = 119–123 | date = August 2011 | url = http://www.australianprescriber.com/magazine/34/4/119/123/new-drugs-962/fampridine | url-status = usurped | archive-url = https://web.archive.org/web/20120227164713/http://www.australianprescriber.com/magazine/34/4/119/123/new-drugs-962/fampridine | archive-date = 2012-02-27 }}</ref> It was undergoing Phase III clinical trials {{as of|2008|lc=on}},<ref>{{cite web | title = Acorda Clinical Development and Product Pipeline | url = http://www.acorda.com/pipeline_fampridine_sci1.asp | website = Acorda }}</ref> and the U.S. Food and Drug Administration (FDA) approved the compound on January 22, 2010.<ref name="FDA">{{cite press release | title = FDA Approves Ampyra to Improve Walking in Adults with Multiple Sclerosis | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm198463.htm | website = U.S. Food and Drug Administration (FDA) | archive-url = https://wayback.archive-it.org/7993/20170112032146/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2010/ucm198463.htm | archive-date = January 12, 2017 }}</ref> 4-AP has been used as treatment for KCNA2-related disorders with gene mutations that show a clear gain-of-function. Benefits include decreased seizures and improved ataxia, alertness, and cognition.<ref name="Hedrich_2021" /> Fampridine is also marketed as '''Ampyra''' (pronounced "am-PEER-ah", according to the maker's website) in the United States by Acorda Therapeutics<ref name="FDA" /><ref>{{cite web | title = Ampyra | url = https://www.nationalmssociety.org/Treating-MS/Medications/Ampyra | website = National Multiple Sclerosis Society }}</ref> and as '''Fampyra''' in the European Union, Canada, and Australia. In Canada, the medication has been approved for use by Health Canada since February 10, 2012.<ref>{{cite web | title = Notice of Decision for FAMPYRA | url = http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/nd_ad_2012_fampyra_132859-eng.php | website = hc-sc.gc.ca | access-date = 2012-04-21 | archive-url = https://web.archive.org/web/20120502012046/http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/nd_ad_2012_fampyra_132859-eng.php | archive-date = 2012-05-02 }}</ref>

==Applications== In the laboratory, 4-AP is a useful pharmacological tool in studying various potassium conductances in physiology and biophysics.{{citation needed|date=January 2018}}<ref>{{cite journal | vauthors = Stühmer W, Ruppersberg JP, Schröter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, Pongs O | title = Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain | journal = The EMBO Journal | volume = 8 | issue = 11 | pages = 3235–3244 | date = November 1989 | pmid = 2555158 | pmc = 401447 | doi = 10.1002/j.1460-2075.1989.tb08483.x }}</ref><ref>{{cite journal | vauthors = Mathie A, Wooltorton JR, Watkins CS | title = Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents | journal = General Pharmacology | volume = 30 | issue = 1 | pages = 13–24 | date = January 1998 | pmid = 9457476 | doi = 10.1016/s0306-3623(97)00034-7 }}</ref> It is a relatively selective blocker of members of Kv1 (Shaker, KCNA) family of voltage-activated K+ channels. However, 4-AP has been shown to potentiate voltage-gated Ca2+ channel currents independent of effects on voltage-activated K+ channels.<ref name="auto">{{cite journal | vauthors = Wu ZZ, Li DP, Chen SR, Pan HL | title = Aminopyridines potentiate synaptic and neuromuscular transmission by targeting the voltage-activated calcium channel beta subunit | journal = The Journal of Biological Chemistry | volume = 284 | issue = 52 | pages = 36453–36461 | date = December 2009 | pmid = 19850918 | pmc = 2794761 | doi = 10.1074/jbc.M109.075523 | doi-access = free }}</ref>

==Convulsant activity== 4-Aminopyridine is a potent convulsant and is used to generate seizures in animal models for the evaluation of antiseizure agents.<ref>{{cite journal | vauthors = Yamaguchi S, Rogawski MA | title = Effects of anticonvulsant drugs on 4-aminopyridine-induced seizures in mice | journal = Epilepsy Research | volume = 11 | issue = 1 | pages = 9–16 | date = March 1992 | pmid = 1563341 | doi = 10.1016/0920-1211(92)90016-m | s2cid = 5772125 }}</ref>

===Vertebrate pesticide=== 4-Aminopyridine is also used under the trade name Avitrol as 0.5% or 1% in bird control bait. It causes convulsions and, infrequently, death, depending on dosage.<ref>{{cite web | title = EPA Reregistration Eligibility Decision for 4-aminopyridine | pages = 23 | date = 27 September 2007 | work = U.S. Environmental Protection Agency | url = https://www3.epa.gov/pesticides/chem_search/reg_actions/reregistration/red_PC-069201_27-Sep-07.pdf }}</ref> The manufacturer says the proper dose should cause epileptic-like convulsions which cause the poisoned birds to emit distress calls resulting in the flock leaving the site; if the dose was sub-lethal, the birds will recover after 4 or more hours without long-term ill effect.<ref name="avitrol">{{cite web | title = What is Avitrol? | url = http://www.avitrol.com/avitrol-a-chemical-agent-to-remove-pest-birds.html | publisher = Avitrol Corporation, Tulsa, Oklahoma, US | access-date = 15 August 2012 }}</ref> The amount of bait should be limited so that relatively few birds are poisoned, causing the remainder of the flock to be frightened away with a minimum of mortality. A lethal dose will usually cause death within an hour.<ref name="avitrol" /> The use of 4-aminopyridine in bird control has been criticized by the Humane Society of the United States.<ref>{{cite web | vauthors = Brasted M | title = Poisonous Solution: The Avitrol Problem | date = May 13, 2008 | url = http://www.hsus.org/wildlife/urban_wildlife_our_wild_neighbors/solving_problems/avitrol.html | publisher = Humane Society of the United States | access-date = December 23, 2008 | archive-url = https://web.archive.org/web/20081225152227/http://www.hsus.org/wildlife/urban_wildlife_our_wild_neighbors/solving_problems/avitrol.html | archive-date = December 25, 2008 | df = mdy-all }}</ref>

===Medical use=== {{Infobox drug | drug_name = Fampridine

| pronounce = | tradename = Ampyra, Fampyra, others | Drugs.com = {{drugs.com|monograph|dalfampridine}} | MedlinePlus = a611005 | DailyMedID = Dalfampridine

| DrugBank_Ref = | DrugBank = DB06637 | NIAID_ChemDB = | PDB_ligand =

| IUPAC_name = 1,4-dihydropyridin-4-imine }}

Fampridine has been used clinically in Lambert–Eaton myasthenic syndrome and multiple sclerosis. It acts by blocking voltage-gated potassium channels, prolonging action potentials and thereby increasing neurotransmitter release at the neuromuscular junction.<ref>{{cite journal | vauthors = Judge SI, Bever CT | title = Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment | journal = Pharmacology & Therapeutics | volume = 111 | issue = 1 | pages = 224–259 | date = July 2006 | pmid = 16472864 | doi = 10.1016/j.pharmthera.2005.10.006 }}</ref> The drug has been shown to reverse saxitoxin and tetrodotoxin toxicity in tissue and animal experiments.<ref name="van_der_Voort_2016">{{cite journal | vauthors = van der Voort PH, Wilffert B, van Roon EN, Uges DR | title = 4-Aminopyridine as a life-saving treatment in calcium channel antagonist intoxication | journal = The Netherlands Journal of Medicine | volume = 74 | issue = 6 | pages = 276 | date = July 2016 | pmid = 27571731 | url = http://www.njmonline.nl/getpdf.php?id=1743 }}</ref><ref name="Chang_1997">{{cite journal | vauthors = Chang FC, Spriggs DL, Benton BJ, Keller SA, Capacio BR | title = 4-Aminopyridine reverses saxitoxin (STX)- and tetrodotoxin (TTX)-induced cardiorespiratory depression in chronically instrumented guinea pigs | journal = Fundamental and Applied Toxicology | volume = 38 | issue = 1 | pages = 75–88 | date = July 1997 | pmid = 9268607 | doi = 10.1006/faat.1997.2328 | s2cid = 17185707 }}</ref><ref name="Chen_1996">{{cite journal | vauthors = Chen HM, Lin CH, Wang TM | title = Effects of 4-aminopyridine on saxitoxin intoxication | journal = Toxicology and Applied Pharmacology | volume = 141 | issue = 1 | pages = 44–48 | date = November 1996 | pmid = 8917674 | doi = 10.1006/taap.1996.0258 }}</ref><ref>[http://www.emedicine.com/emerg/topic342.htm Octopus Envenomations] at eMedicine.com</ref> In calcium entry blocker overdose in humans, 4-aminopyridine can increase the cytosolic Ca2+ concentration very efficiently independent of the calcium channels.<ref name="van_der_Voort_2016" />

====Multiple sclerosis==== Fampridine has been shown to improve visual function and motor skills and relieve fatigue in patients with multiple sclerosis (MS). However, the effect of the drug is strongly established for walking capacity only.<ref>{{cite journal | vauthors = Valet M, Quoilin M, Lejeune T, Stoquart G, Van Pesch V, El Sankari S, Detrembleur C, Warlop T | title = Effects of Fampridine in People with Multiple Sclerosis: A Systematic Review and Meta-analysis | journal = CNS Drugs | volume = 33 | issue = 11 | pages = 1087–1099 | date = November 2019 | pmid = 31612418 | doi = 10.1007/s40263-019-00671-x | hdl-access = free | s2cid = 204543081 | hdl = 2078.1/220661 }}</ref> Common side effects include dizziness, nervousness and nausea, and the incidence of adverse effects was shown to be less than 5% in all studies.<ref>{{Citation | date = 1 Jun 2017 | title = Fampyra: EPAR - Product Information | publisher = European Medicines Agency | location = London | url = http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002097/WC500109956.pdf | access-date = 11 Feb 2018 | archive-date = 11 February 2018 | archive-url = https://web.archive.org/web/20180211131458/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002097/WC500109956.pdf }}</ref><ref name="Fampyra EPAR">{{cite web | title = Fampyra EPAR | date = 17 September 2018 | website = European Medicines Agency (EMA) | url = https://www.ema.europa.eu/en/medicines/human/EPAR/fampyra | access-date = 24 August 2020 }}</ref>

4-AP works as a potassium channel blocker. Strong potassium currents decrease action potential duration and amplitude, which increases the probability of conduction failure − a well documented characteristic of demyelinated axons. Potassium channel blockade has the effect of increasing axonal action potential propagation and improving the probability of synaptic vesicle release. A study has shown that 4-AP is a potent calcium channel activator and can improve synaptic and neuromuscular function by directly acting on the calcium channel beta subunit.<ref name="auto"/>

MS patients treated with 4-AP exhibited a response rate of 29.5% to 80%. A long-term study (32 months) indicated that 80-90% of patients who initially responded to 4-AP exhibited long-term benefits. Although improving symptoms, 4-AP does not inhibit progression of MS. Another study, conducted in Brazil, showed that treatment based on fampridine was considered efficient in 70% of the patients.<ref>{{Cite journal | title = Real-life experience with fampridine (Fampyra) for patients with multiple sclerosis and gait disorders | journal = NeuroRehabilitation | date = August 1, 2016 }}</ref>

====Spinal cord injury====

Spinal cord injury patients have also seen improvement with 4-AP therapy. These improvements include sensory, motor and pulmonary function, with a decrease in spasticity and pain.<ref>{{cite journal | vauthors = Van Diemen HA, Polman CH, Koetsier JC, Van Loenen AC, Nauta JJ, Bertelsmann FW | title = 4-Aminopyridine in patients with multiple sclerosis: dosage and serum level related to efficacy and safety | journal = Clinical Neuropharmacology | volume = 16 | issue = 3 | pages = 195–204 | date = June 1993 | pmid = 8504436 | doi = 10.1097/00002826-199306000-00002 }}</ref>

==== KCNA2-related disorders ==== 4-Aminopyridine is a gene-targeted therapy option for KCNA2-related disorders with a gain-of-function (GOF) or some mix-of-function (MOF) gene mutations.<ref name="Hedrich_2021">{{cite journal | vauthors = Hedrich UB, Lauxmann S, Wolff M, Synofzik M, Bast T, Binelli A, Serratosa JM, Martínez-Ulloa P, Allen NM, King MD, Gorman KM, Zeev BB, Tzadok M, Wong-Kisiel L, Marjanovic D, Rubboli G, Sisodiya SM, Lutz F, Ashraf HP, Torge K, Yan P, Bosselmann C, Schwarz N, Fudali M, Lerche H | title = 4-Aminopyridine is a promising treatment option for patients with gain-of-function ''KCNA2''-encephalopathy | journal = Science Translational Medicine | volume = 13 | issue = 609 | article-number = eaaz4957 | date = September 2021 | pmid = 34516822 | doi = 10.1126/scitranslmed.aaz4957 }}</ref><ref name="Gao_2025">{{Cite journal | vauthors = Gao L, Jia Y, Yang Y, Chen J, Ren L | title = Aminopyridine treatment for an adult case of developmental and epileptic encephalopathy with a gain-of-function mutation in KCNA2 | journal = Genes & Diseases | date = 2025-08-07 | doi = 10.1016/j.gendis.2025.101798 | url = https://www.sciencedirect.com/science/article/pii/S2352304225002879 | article-number = 101798 | issn = 2352-3042 | doi-access = free }}</ref> It has shown to improve seizure control, gait, ataxia, alertness, and cognition.<ref name="Hedrich_2021" /> GOF KCNA2 disorders are caused by voltage-gated potassium channels in the central nervous system that stay open and allow too much flow of potassium currents.<ref>{{cite journal | vauthors = Syrbe S, Hedrich UB, Riesch E, Djémié T, Müller S, Møller RS, Maher B, Hernandez-Hernandez L, Synofzik M, Caglayan HS, Arslan M, Serratosa JM, Nothnagel M, May P, Krause R, Löffler H, Detert K, Dorn T, Vogt H, Krämer G, Schöls L, Mullis PE, Linnankivi T, Lehesjoki AE, Sterbova K, Craiu DC, Hoffman-Zacharska D, Korff CM, Weber YG, Steinlin M, Gallati S, Bertsche A, Bernhard MK, Merkenschlager A, Kiess W, Gonzalez M, Züchner S, Palotie A, Suls A, De Jonghe P, Helbig I, Biskup S, Wolff M, Maljevic S, Schüle R, Sisodiya SM, Weckhuysen S, Lerche H, Lemke JR | title = De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy | journal = Nature Genetics | volume = 47 | issue = 4 | pages = 393–399 | date = April 2015 | pmid = 25751627 | pmc = 4380508 | doi = 10.1038/ng.3239 }}</ref> Some MOF KCNA2 disorders also act like GOF in regards to their flow of potassium through the channel which is why they may also benefit from 4-AP therapy.<ref>{{cite journal | vauthors = Imbrici P, Conte E, Blunck R, Stregapede F, Liantonio A, Tosi M, D'Adamo MC, De Luca A, Brankovic V, Zanni G | title = A Novel ''KCNA2'' Variant in a Patient with Non-Progressive Congenital Ataxia and Epilepsy: Functional Characterization and Sensitivity to 4-Aminopyridine | journal = International Journal of Molecular Sciences | volume = 22 | issue = 18 | pages = 9913 | date = September 2021 | pmid = 34576077 | pmc = 8469797 | doi = 10.3390/ijms22189913 | doi-access = free }}</ref> 4-AP acts by closing these channels and improves the natural flow of potassium through the neuron.<ref name="Hedrich_2021" />

As of 2025 the use of 4-AP for KCNA2 is in an experimental stage, but it has shown significant improvement for most patients that have used it. Out of 13 documented patients, eight became seizure free, two others experienced a reduction in seizures, and 11 had improved gait, ataxia, alertness, cognition, or speech.<ref>{{Cite web | vauthors = Albert H | title = Potential Treatment for Rare Genetic Epilepsy Discovered | date = 2021-09-02 | url = https://www.insideprecisionmedicine.com/news-and-features/potential-treatment-for-rare-genetic-epilepsy-discovered/ | access-date = 2025-12-03 | website = Inside Precision Medicine | language = en-US }}</ref><ref name="Gao_2025" /><ref>{{Cite web | title = use of 4-aminopyridine in kcna2 epilepsy and neurodevelopmental disorder | url = https://aesnet.org/abstractslisting/use-of-4-aminopyridine-in-kcna2-epilepsy-and-neurodevelopmental-disorder | access-date = 2025-12-03 | website = Default }}</ref> Only one patient experienced side effects of increased seizures and no other symptoms were reported.<ref name="Hedrich_2021" />

Authors of the first 4-AP KCNA2 study created an online tool to guide physicians in identifying which KCNA2 patients would benefit from this therapy. It is publicly accessible due to the importance for treating this disease from young age. See the article for details on accessing this information.<ref name="Hedrich_2021" />

====Tetrodotoxin poisoning==== Clinical studies have shown that 4-AP is capable of reversing the effects of tetrodotoxin poisoning in animals, however, its effectiveness as an antidote in humans has not yet been determined.<ref name="van_der_Voort_2016" /><ref name="Chang_1997" /><ref name="Chen_1996" />

===Overdose=== Case reports have shown that overdoses with 4-AP can lead to paresthesias, seizures,<ref>{{cite journal | vauthors = Pickett TA, Enns R | title = Atypical presentation of 4-aminopyridine overdose | journal = Annals of Emergency Medicine | volume = 27 | issue = 3 | pages = 382–385 | date = March 1996 | pmid = 8599505 | doi = 10.1016/S0196-0644(96)70277-9 }}</ref> and atrial fibrillation.<ref>{{cite journal | vauthors = Johnson NC, Morgan MW | title = An unusual case of 4-aminopyridine toxicity | journal = The Journal of Emergency Medicine | volume = 30 | issue = 2 | pages = 175–177 | date = February 2006 | pmid = 16567254 | doi = 10.1016/j.jemermed.2005.04.020 }}</ref>

==Contraindications== 4-aminopyridine is excreted by the kidneys. 4-AP should not be given to people with significant kidney disease (e.g., acute kidney injury or advanced chronic kidney disease) due to the higher risk of seizures with increased circulating levels of 4-AP.

==Branding== The drug was originally intended, by Acorda Therapeutics, to have the brand name ''Amaya'', however the name was changed to ''Ampyra'' to avoid potential confusion with other marketed pharmaceuticals.<ref>{{cite news | vauthors = Jeffrey S | title = FDA Approves Dalfampridine to Improve Walking in Multiple Sclerosis | date = January 22, 2010 | url = http://www.medscape.com/viewarticle/715722 | work = Medscape }}</ref>

Four of Acorda's patents pertaining to Ampyra were invalidated in 2017 by the United States District Court for the District of Delaware and a fifth patent expired in 2018.<ref name="US courts invalidate Dalfampridine patents">{{cite web | title = US courts invalidates Dalfampridine patents | url = http://ir.acorda.com/investors/investor-news/investor-news-details/2018/US-Court-of-Appeals-for-the-Federal-Circuit-Upholds-District-Courts-Decision-to-Invalidate-AMPYRA-dalfampridine-Patents/default.aspx | website = Acorda | access-date = 2018-11-25 | archive-date = 2020-09-15 | archive-url = https://web.archive.org/web/20200915072630/http://ir.acorda.com/investors/investor-news/investor-news-details/2018/US-Court-of-Appeals-for-the-Federal-Circuit-Upholds-District-Courts-Decision-to-Invalidate-AMPYRA-dalfampridine-Patents/default.aspx }}</ref> Since then, generic alternatives have been developed for the U.S. market.<ref>{{cite news | vauthors = House DW | title = Supreme Court declines to hear Acorda appeal of adverse Ampyra patent ruling | date = 7 October 2019 | url = https://seekingalpha.com/news/3504200-supreme-court-declines-hear-acorda-appeal-adverse-ampyra-patent-ruling | website = Seeking Alpha | access-date = 8 October 2019 | language = en }}</ref>

The drug is marketed by Biogen Idec in Canada as ''Fampyra''<ref name="FampyraMonograph">{{cite web | title = Fampyra Drug Monograph | date = 26 November 2014 | url = https://pdf.hres.ca/dpd_pm/00028384.PDF | website = Health Canada Drug Product Database | publisher = Biogen Idec Canada Inc. | access-date = 10 October 2017 }}</ref> and as ''Dalstep'' in India by Sun Pharma.<ref name="Dalstep 10mg">{{cite web | title = Dalstep 10mg Registration Details | url = https://www.registrationwala.com/trademark/3613942-dalstep | website = Registrationwala | access-date = 2018-11-25 | archive-date = 2020-09-15 | archive-url = https://web.archive.org/web/20200915071209/https://www.registrationwala.com/trademark/3613942-dalstep }}</ref>

== Research == === Parkinson's disease ===

Dalfampridine completed Phase II clinical trials for Parkinson's disease in July 2014.<ref>{{ClinicalTrialsGov|NCT01491022|A Randomized Trial to Evaluate Ampyra for Gait Impairment in Parkinson's Disease}}</ref>{{update inline|date=August 2020}}

== See also == *4-Dimethylaminopyridine, a popular laboratory reagent, is prepared directly from pyridine instead of via methylating this compound.<ref name=Ullmann>Shinkichi Shimizu, Nanao Watanabe, Toshiaki Kataoka, Takayuki Shoji, Nobuyuki Abe, Sinji Morishita, Hisao Ichimura "Pyridine and Pyridine Derivatives" in "Ullmann's Encyclopedia of Industrial Chemistry" 2007; John Wiley & Sons: New York.</ref> *Pyridine *4-Pyridylnicotinamide, useful as a ligand in coordination chemistry, is prepared by the reaction of this compound with nicotinoyl chloride.<ref>{{Cite journal | vauthors = Gardner TS, Wenis E, Lee J | title = The Synthesis of Compounds for the Chemotherapy of Tuberculosis. Iv. The Amide Function | journal = The Journal of Organic Chemistry | volume = 19 | issue = 5 | pages = 753 | year = 1954 | doi = 10.1021/jo01370a009 }}</ref>

== References == {{reflist}}

{{DEFAULTSORT:Aminopyridine, 4-}} Category:Highly-toxic chemical substances Category:Potassium channel blockers Category:Orphan drugs Category:Avicides X Category:4-Aminopyridines Category:4-Pyridyl compounds