{{Short description|Stimulant, used in the treatment of ADHD}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Verifiedfields = changed | class = [[Stimulant]];<br /> [[Dopamine reuptake inhibitor]];<br /> [[Dopamine releasing agent]] | verifiedrevid = 461086403 | IUPAC_name = (''RS'')-2-amino-5-phenyl-1,3-oxazol-4(5''H'')-one | image = Pemoline structure 2.svg | image_class = skin-invert-image | width = 175px | image2 = File:Pemoline ball-and-stick model.png | image_class2 = bg-transparent | width2 = 175px | chirality = [[Racemic mixture]]
<!--Clinical data-->| tradename = Cylert, others | Drugs.com = {{drugs.com|CONS|pemoline}} | pregnancy_US = B | legal_AU = S4 | legal_BR = B1 | legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |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=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref> | legal_CA = Schedule IV | legal_DE = Rx-only/Anlage III | legal_US = Schedule IV | routes_of_administration = [[Oral administration|By mouth]]<ref name="PatrickMarkowitz1997" /><ref name="Cylert-Label" />
<!--Pharmacokinetic data-->| bioavailability = | protein_bound = ≤50%<ref name="Cylert-Label" /><ref name="PatrickMarkowitz1997" /> | metabolism = [[Liver]]<ref name="Cylert-Label" /> | metabolites = Various<ref name="Cylert-Label" /> | elimination_half-life = 7–12 hours<ref name="PatrickMarkowitz1997" /><ref name="Cylert-Label" /> | excretion = Mainly [[urine]]<ref name="Cylert-Label" />
<!--Identifiers-->| CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 2152-34-3 | ATC_prefix = N06 | ATC_suffix = BA05 | PubChem = 4723 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01230 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4561 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 7953 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 7GAQ2332NK | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00744 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1177 | synonyms = Pheniminooxazolidinone; Phenylisohydantoin; Phenylpseudohydantoin; Phenilone; 2-Imino-5-phenyl-4-oxazolidinone; 2-Amino-5-phenyl-1,3-oxazol-4(5H)-one
<!--Chemical data-->| C = 9 | H = 8 | N = 2 | O = 2 | SMILES = O=C2\N=C(/OC2c1ccccc1)N | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C9H8N2O2/c10-9-11-8(12)7(13-9)6-4-2-1-3-5-6/h1-5,7H,(H2,10,11,12) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = NRNCYVBFPDDJNE-UHFFFAOYSA-N }}
'''Pemoline''', formerly sold under the brand name '''Cylert''' among others, is a [[stimulant]] medication which was used in the treatment of [[attention-deficit hyperactivity disorder|attention deficit hyperactivity disorder]] (ADHD) and [[narcolepsy]].<ref name="Cylert-Label" /> It has since been discontinued in most countries due to rare but serious [[liver toxicity]].<ref name="pmid18830438">{{cite journal | vauthors = Billiard M | title = Narcolepsy: current treatment options and future approaches | journal = Neuropsychiatr Dis Treat | volume = 4 | issue = 3 | pages = 557–66 | date = June 2008 | pmid = 18830438 | pmc = 2526380 | doi = | url = }}</ref><ref name="pmid28366595">{{cite journal | vauthors = Shader RI | title = Risk Evaluation and Mitigation Strategies (REMS), Pemoline, and What Is a Signal? | journal = Clin Ther | volume = 39 | issue = 4 | pages = 665–669 | date = April 2017 | pmid = 28366595 | doi = 10.1016/j.clinthera.2017.03.008 | url = | doi-access = free }}</ref> The medication was taken [[oral administration|by mouth]].<ref name="Cylert-Label" />
Common [[side effect]]s include [[insomnia]], [[decreased appetite]], [[abdominal pain]], [[irritability]], and [[headache]]s,<ref name="PatrickMarkowitz1997" /><ref name="Cylert-Label" /> while rare cases of serious [[hepatotoxicity|liver damage]] requiring [[liver transplantation]] or causing death have been reported.<ref name="pmid11865963">{{cite journal | vauthors = Nakamura H, Blumer JL, Reed MD | title = Pemoline ingestion in children: a report of five cases and review of the literature | journal = J Clin Pharmacol | volume = 42 | issue = 3 | pages = 275–82 | date = March 2002 | pmid = 11865963 | doi = 10.1177/00912700222011292 | s2cid = 27024140 | url = }}</ref><ref name="pmid11392339">{{cite journal | vauthors = Safer DJ, Zito JM, Gardner JE | title = Pemoline hepatotoxicity and postmarketing surveillance | journal = J Am Acad Child Adolesc Psychiatry | volume = 40 | issue = 6 | pages = 622–9 | date = June 2001 | pmid = 11392339 | doi = 10.1097/00004583-200106000-00006 | url = }}</ref> As a stimulant, pemoline acts as a [[binding selectivity|selective]] [[dopamine reuptake inhibitor]] and [[dopamine releasing agent|releasing agent]]<ref name="PatrickMarkowitz1997" /><ref name="pmid9185233" /><ref name="Cylert-Label" /><ref name="Fuller_1978" /> via indirect [[agonist|agonism]] of [[dopamine receptor]]s.<ref name="pmid9708845" /> In addition, it shows little activity with respect to [[norepinephrine]], thus minimal to no [[cardiovascular]] or [[sympathomimetic]] effects in comparison to many other stimulants.<ref name="PatrickMarkowitz1997" /><ref name="pmid9185233" /><ref name="Cylert-Label" />
Pemoline was first synthesized in 1913, but its stimulant activity was not discovered until the 1930s, nor used for ADHD until 1975.<ref name="ChemischeBerichte1913" /><ref name="ActaAcademiaeAboensis1939" /><ref name="PatrickMarkowitz1997" /> Between 1997 and 2005, many countries, including the United States, [[withdrawn drug|withdrew]] the drug due to liver toxicity.<ref name="pmid18793403" /><ref name="pmid11392339" /><ref name="pmid18217792" /> However, it remains available in Japan for the treatment of narcolepsy at lower doses than those used for ADHD.<ref name="pmid28366595" /> Pemoline is a [[Controlled Substances Act#Schedule IV controlled substances|schedule IV]] [[controlled substance]] in the United States due to structural and functional similarity to other stimulants, and [[potential for misuse]].<ref name="INCB" /><ref name="CRC2014" /> However, it is noted to have less misuse potential than other stimulant drugs.<ref name="PatrickMarkowitz1997" />
==Medical uses== Pemoline has been used in the treatment of ADHD and narcolepsy.<ref name="Cylert-Label" /><ref name="PatrickMarkowitz1997" /><ref name="pmid28366595" /> It has also been used in the treatment of [[excessive daytime sleepiness]].<ref name="pmid9185233">{{cite journal | vauthors = Nishino S, Mignot E | title = Pharmacological aspects of human and canine narcolepsy | journal = Prog Neurobiol | volume = 52 | issue = 1 | pages = 27–78 | date = May 1997 | pmid = 9185233 | doi = 10.1016/s0301-0082(96)00070-6 | s2cid = 31839355 | url = | doi-access = free }}</ref> The medication was typically used at doses of 18.75 to 112.5{{nbsp}}mg once per day in the treatment of ADHD, with the effective dose for most people being in the range of 56.25 to 75{{nbsp}}mg.<ref name="PatrickMarkowitz1997" /><ref name="Cylert-Label" /> The [[onset of action]] of pemoline is gradual and therapeutic benefits may not occur until the third or fourth weeks of use.<ref name="Cylert-Label" /><ref name="PatrickMarkowitz1997" /> This may be due to a cautious low initial starting dose of 37.5{{nbsp}}mg and gradual titration in dose upwards over several weeks.<ref name="PatrickMarkowitz1997" />
===Available forms=== Pemoline was available in the form of 18.75, 37.5, and 75{{nbsp}}mg [[oral administration|oral]] [[immediate-release]] [[tablet (pharmacy)|tablet]]s (Cylert) as well as 37.5{{nbsp}}mg oral immediate-release [[chewable tablet]]s.<ref name="PatrickMarkowitz1997" /><ref name="Cylert-Label" /> It was provided mainly in the form of the free base but also as the [[magnesium]] [[salt (chemistry)|salt]].<ref name="SwissPharmaceuticalSociety2000" />
==Side effects== [[Side effect]]s of pemoline include [[insomnia]], [[decreased appetite]], [[abdominal pain]], [[irritability]], and [[headache]]s.<ref name="PatrickMarkowitz1997" /><ref name="Cylert-Label" /> It has minimal [[cardiovascular]] or [[sympathomimetic]] side effects.<ref name="PatrickMarkowitz1997" /><ref name="Cylert-Label" /> Pemoline is described as a lower-efficacy/milder stimulant than classical stimulants like [[amphetamine]]s and [[methylphenidate]] and is said to have fewer side effects than them.<ref name="NishinoKotorii2016">{{cite book | title = Narcolepsy | vauthors = Nishino S, Kotorii N | chapter = Overview of Management of Narcolepsy | date = 2016 | pages = 285–305 | publisher = Springer International Publishing | doi = 10.1007/978-3-319-23739-8_21 | isbn = 978-3-319-23738-1 | url = }}</ref>
===Liver toxicity=== Rarely, pemoline is implicated in causing [[hepatotoxicity]].<ref name="PatrickMarkowitz1997" /><ref name="pmid9602211">{{cite journal |vauthors=Marotta PJ, Roberts EA |title=Pemoline hepatotoxicity in children |journal=J. Pediatr. |volume=132 |issue=5 |pages=894–7 |date=May 1998 |pmid=9602211 |doi=10.1016/S0022-3476(98)70329-4 }}</ref> Because of this, the FDA recommended that regular liver tests be performed in those treated with it.<ref name="pmid12108802">{{cite journal |vauthors=Willy ME, Manda B, Shatin D, Drinkard CR, Graham DJ |title=A study of compliance with FDA recommendations for pemoline (Cylert) |journal=J Am Acad Child Adolesc Psychiatry |volume=41 |issue=7 |pages=785–90 |date=July 2002 |pmid=12108802 |doi=10.1097/00004583-200207000-00009 |url=https://zenodo.org/record/1234804 |access-date=2020-09-10 |archive-date=2021-05-31 |archive-url=https://web.archive.org/web/20210531152527/https://zenodo.org/record/1234804 |url-status=live }}</ref> Since being introduced, it has been linked with at least 21 cases of [[liver failure]], of which 13 resulted in liver replacement or death. Approximately 1–2% of patients taking the drug show elevated levels of liver [[transaminase]] enzymes, a marker for liver toxicity, though serious cases are rare. Over 200,000 children with ADHD were prescribed pemoline in the United States and Canada alone during the approximate 25 years that it was available, plus a smaller number of adults prescribed it for other indications (and not including prescriptions in the rest of the world). As such, the number of liver failure cases was statistically not that large. However the reactions proved idiosyncratic and unpredictable, with patients sometimes taking the drug with no issue for months or even years, before suddenly developing severe liver toxicity. There was no clear exposure–toxicity relationship, and no characteristic liver [[pathology]] findings. Some patients showed as little as one week between first appearance of [[jaundice]] and complete liver failure, and some of the patients that developed liver failure had not showed elevated liver transaminase levels when tested previously.<ref name="pmid18217792">{{cite journal |vauthors=Etwel FA, Rieder MJ, Bend JR, Koren G |title=A surveillance method for the early identification of idiosyncratic adverse drug reactions |journal=Drug Saf |volume=31 |issue=2 |pages=169–80 |year=2008 |pmid=18217792 |doi= 10.2165/00002018-200831020-00006|s2cid=19964105 }}</ref> On the other hand, there are no cases of liver failure associated with pemoline in Japan, although it is used at lower doses and is only prescribed for the niche indication of narcolepsy in this country.<ref name="pmid28366595" />
==Overdose== Overdose of pemoline may present with [[choreoathetosis]] symptoms.<ref>{{cite journal |vauthors=Stork CM, Cantor R |title=Pemoline induced acute choreoathetosis: case report and review of the literature |journal=J. Toxicol. Clin. Toxicol. |volume=35 |issue=1 |pages=105–8 |year=1997 |pmid=9022662 |doi= 10.3109/15563659709001175}}</ref>
==Interactions== Other stimulants and [[monoamine oxidase inhibitor]]s are [[contraindication|contraindicated]] with pemoline.{{citation needed|date=November 2024}}
==Pharmacology==
===Pharmacodynamics=== The [[pharmacodynamics]] of pemoline are poorly understood and its precise [[mechanism of action]] hasn't been definitively determined.<ref name="PatrickMarkowitz1997" /><ref name="Cylert-Label">{{cite web|title=Cylert (Pemoline)|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/016832s022_017703s018lbl.pdf|publisher=FDA|access-date=15 February 2014|date=December 2002|archive-date=4 March 2016|archive-url=https://web.archive.org/web/20160304002256/http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/016832s022_017703s018lbl.pdf|url-status=dead}}</ref> However, pemoline has similar activity and effects to those of other [[psychostimulant]]s, and in animals the medication appears to act as a [[dopamine reuptake inhibitor]] and [[dopamine releasing agent|releasing agent]].<ref name="PatrickMarkowitz1997" /> By increasing dopamine levels in the brain, it functions as an indirect [[agonist]] of [[dopamine receptor]]s.<ref name="pmid9708845">{{cite journal | vauthors = Solanto MV | title = Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration | journal = Behav Brain Res | volume = 94 | issue = 1 | pages = 127–52 | date = July 1998 | pmid = 9708845 | doi = 10.1016/s0166-4328(97)00175-7 | s2cid = 11110885 | url = }}</ref> In contrast to most other stimulants, pemoline appears to produce no significant [[central nervous system|central]] or [[periphery (body)|peripheral]] [[noradrenergic]] effects.<ref name="PatrickMarkowitz1997" /> As a result, it has minimal or no [[cardiovascular]] or [[sympathomimetic]] effects.<ref name="PatrickMarkowitz1997" /> Pemoline is described as a [[binding selectivity|selective]] dopamine reuptake inhibitor that only weakly stimulates dopamine release.<ref name="pmid9185233" /><ref name="Fuller_1978">{{cite journal | vauthors = Fuller RW, Perry KW, Bymaster FP, Wong DT | title = Comparative effects of pemoline, amfonelic acid and amphetamine on dopamine uptake and release in vitro and on brain 3,4-dihydroxyphenylacetic acid concentration in spiperone-treated rats | journal = The Journal of Pharmacy and Pharmacology | volume = 30 | issue = 3 | pages = 197–198 | date = March 1978 | pmid = 24701 | doi = 10.1111/j.2042-7158.1978.tb13201.x }}</ref>
While drugs like [[dextroamphetamine]] and [[methylphenidate]] are classified as [[Controlled Substances Act#Schedule II controlled substances|schedule II]] and have considerable misuse potential, pemoline is listed as [[Controlled Substances Act#Schedule IV controlled substances|schedule IV]] (non-narcotic).<ref name="Cylert-Label" /> In studies conducted on primates, pemoline fails to demonstrate a potential for self-administration.<ref name="Cylert-Label" /> It is thought to have little potential for abuse and dependence.<ref name="PatrickMarkowitz1997" /> Nonetheless, misuse may theoretically occur owing to its similarity to other psychostimulants.<ref name="Cylert-Label" />
===Pharmacokinetics=== Studies of the [[pharmacokinetics]] of pemoline in humans are very limited.<ref name="PatrickMarkowitz1997" /> The [[Tmax (pharmacology)|time to peak levels]] of pemoline is 2 to 4{{nbsp}}hours.<ref name="Cylert-Label" /><ref name="PatrickMarkowitz1997">{{cite journal | vauthors = Patrick KS, Markowitz JS | title = Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention-deficit hyperactivity disorder | journal = Human Psychopharmacology: Clinical and Experimental | date = November 1997 | volume = 12 | issue = 6 | pages = 527–546 | issn = 0885-6222 | eissn = 1099-1077 | doi = 10.1002/(SICI)1099-1077(199711/12)12:6<527::AID-HUP932>3.0.CO;2-U | pmid = | s2cid = 144548631 | url = }}</ref> [[Cmax (pharmacology)|Peak levels]] have been reported to be in the range of 2 to 4.5{{nbsp}}μg/mL.<ref name="PatrickMarkowitz1997" /> [[Steady state (pharmacokinetics)|Steady-state levels]] of pemoline are reached in 2 to 3{{nbsp}}days.<ref name="Cylert-Label" />
Pemoline is variously reported to have no significant [[plasma protein binding]] or to have 50% plasma protein binding.<ref name="PatrickMarkowitz1997" /><ref name="Cylert-Label" />
Pemoline is [[metabolism|metabolized]] in the [[liver]].<ref name="Cylert-Label" /> Its [[metabolite]]s include pemoline conjugate, pemoline dione, mandelic acid, and unidentified polar metabolites.<ref name="Cylert-Label" />
Pemoline is [[excretion|excreted]] mainly by the [[kidney]]s with around 50% excreted in unchanged form and only minor amounts present as metabolites.<ref name="Cylert-Label" /> The [[elimination half-life]] of pemoline is 7 to 12{{nbsp}}hours.<ref name="PatrickMarkowitz1997" /><ref name="Cylert-Label" /> The half-life is 7{{nbsp}}hours in children but may increase to 11 to 12{{nbsp}}hours with age.<ref name="PatrickMarkowitz1997" /> The relatively long half-life of pemoline allows for once-daily administration.<ref name="PatrickMarkowitz1997" />
No differences in the pharmacokinetics of pemoline were found with conventional tablets, chewable tablets swallowed, or chewable tablets chewed.<ref name="PatrickMarkowitz1997" />
==Chemistry== Pemoline is a member of the 4-[[oxazolidinone]] class and is structurally related to other members of the class including [[aminorex]], [[4-methylaminorex]], [[clominorex]], [[cyclazodone]], [[fenozolone]], [[fluminorex]], and [[thozalinone]].
The salts of pemoline in use are pemoline magnesium (free base conversion ratio .751), pemoline iron (.578), pemoline copper (.644), pemoline nickel (.578), pemoline rubidium, pemoline calcium, pemoline chromium, and chelates of the above which are identical in weight to the salt mentioned. Pemoline free base and pemoline cobalt, strontium, silver, barium, lithium, sodium, potassium, zinc, manganese, and caesium are research chemicals which can be produced in situ for experiments.<ref name="CRC2014">DEA office of Diversion Control site: Federal Register publications of CSA schedules, 2014 Q1</ref><ref>The A-Z Encyclopaedia of Alcohol and Drug Abuse</ref><ref>CRC Handbook of Chemistry & Physics</ref> Others such as lanthanide pemoline salts such as pemoline cerium can be prepared; pemoline beryllium would presumably be toxic.
==History== Pemoline was first synthesized in 1913<ref name="Elks2014" /><ref name="ChemischeBerichte1913">Chemische Berichte, 1913, vol.46, p. 2083</ref> but its activity was not discovered until the 1930s.<ref name="ActaAcademiaeAboensis1939">Acta Academiae Aboensis, Series B: Mathematica et Physica, 1939, vol. 11, #14 p. 3,7</ref> Pemoline was approved for the treatment of ADHD in the United States in 1975.<ref name="PatrickMarkowitz1997" /><ref name="pmid28366595" />
Cases of serious liver toxicity and associated death related to pemoline in children and adolescents were reported to the [[United States]] [[Food and Drug Administration]]'s [[MedWatch]] between 1977 and 1996.<ref name="pmid11392339" /> Serious liver toxicity with pemoline was first described in the medical literature in 1984 and 1989 [[letter to the editor|letters to the editor]].<ref name="pmid11392339" /> Clinicians were little-aware of liver toxicity with pemoline until the 1990s.<ref name="pmid11392339" /> Warnings for liver toxicity for pemoline were added to the [[United States]] [[Food and Drug Administration]] (FDA) label for the medication in December 1996 and a [[black box warning]] was added in June 1999 along with requirements for written consent and frequent monitoring of [[liver enzyme]]s.<ref name="pmid18793403">{{cite journal | vauthors = Zito JM, Derivan AT, Kratochvil CJ, Safer DJ, Fegert JM, Greenhill LL | title = Off-label psychopharmacologic prescribing for children: history supports close clinical monitoring | journal = Child Adolesc Psychiatry Ment Health | volume = 2 | issue = 1 | article-number = 24 | date = September 2008 | pmid = 18793403 | pmc = 2566553 | doi = 10.1186/1753-2000-2-24 | url = | doi-access = free }}</ref><ref name="pmid18217792" /><ref name="pmid11392339"/> These warnings followed a 1995 publication on liver toxicity with pemoline.<ref name="pmid11392339" /><ref name="pmid7781270">{{cite journal | vauthors = Berkovitch M, Pope E, Phillips J, Koren G | title = Pemoline-associated fulminant liver failure: testing the evidence for causation | journal = Clin Pharmacol Ther | volume = 57 | issue = 6 | pages = 696–8 | date = June 1995 | pmid = 7781270 | doi = 10.1016/0009-9236(95)90233-3 | s2cid = 37312352 | url = }}</ref> However, findings suggested that clinicians poorly followed the FDA's directives on use of pemoline.<ref name="pmid18793403" /> In any case, sales of pemoline in the United States increased until 1997 and declined between 1996 and 1999.<ref name="pmid11392339" /> Pemoline was [[withdrawn drug|withdrawn]] due to liver toxicity in the [[United Kingdom]] in September 1997, in [[Canada]] in September 1999, and in the United States in 2005.<ref name="pmid18793403" /><ref name="pmid16981848">{{cite journal | vauthors = Shah RR | title = Can pharmacogenetics help rescue drugs withdrawn from the market? | journal = Pharmacogenomics | volume = 7 | issue = 6 | pages = 889–908 | date = September 2006 | pmid = 16981848 | doi = 10.2217/14622416.7.6.889 | url = }}</ref><ref name="pmid18217792" /><ref name="pmid11392339" /> Abbott Laboratories voluntarily withdrew pemoline from the United States market in May 2005 and the FDA withdrew approval of generic pemoline in November 2005.<ref name="pmid18793403" /><ref name="pmid18217792" /> Pemoline remains available in Japan for treatment of narcolepsy as of 2017.<ref name="pmid28366595" />
==Society and culture==
===Names=== ''Pemoline'' is the [[generic term|generic name]] of the drug and its {{Abbrlink|INN|International Nonproprietary Name}}, {{Abbrlink|USAN|United States Adopted Name}}, and {{Abbrlink|BAN|British Approved Name}}.<ref name="Elks2014">{{cite book | veditors = Elks J | date = 14 November 2014 | title = The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher = Springer | pages = 70– | isbn = 978-1-4757-2085-3 | oclc = 1058412474 | url = https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA70}}</ref><ref name="SwissPharmaceuticalSociety2000" />
Pemoline was formerly marketed under the brand names Cylert, Betanamin, Ceractiv, Hyperilex, Kethamed, Ronyl, Stimul, Tamilan, Tradon, Tropocer, and Volital.<ref name="SwissPharmaceuticalSociety2000" /><ref name="Kar2005">{{cite book | author = Ashutosh Kar | date = 2005 | title = Medicinal Chemistry | publisher = New Age International | pages = 201– | isbn = 9788122415650 | oclc = 818800751 | url = https://books.google.com/books?id=07g30rxCA0EC&pg=PA201}}</ref><ref name="Elks2014" />
===Availability=== Pemoline has been marketed in the United States, Canada, the United Kingdom, Belgium, Luxembourg, Spain, Germany, Switzerland, Japan and Argentina.<ref name="SwissPharmaceuticalSociety2000">{{cite book | editor = Swiss Pharmaceutical Society | author = Swiss Pharmaceutical Society | date = 2000 | title = Index Nominum 2000: International Drug Directory | publisher = Taylor & Francis | pages = 799– | isbn = 978-3-88763-075-1 | url = https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA799}}</ref> It remains available in Japan for the treatment of narcolepsy as of 2017.<ref name="pmid28366595" /> However, the medication is said to be rarely used in Japan as narcolepsy is a niche indication and as clinicians are wary of the liver toxicity that it has been associated with.<ref name="pmid28366595" /><ref name="Takeda2009">{{cite journal | vauthors = Takeda T | title = Psychopharmacology for attention-deficit/hyperactivity disorder in Japan | journal = Current Attention Disorders Reports | date = March 2009 | volume = 1 | issue = 1 | pages = 21–28 | issn = 1943-4561 | eissn = 1943-457X | doi = 10.1007/s12618-009-0004-5 | pmid = | s2cid = 3559647 | url = }}</ref>
===Legal status=== Under the [[Convention on Psychotropic Substances]], it is a [[Controlled Substances Act#Schedule IV|schedule IV]] [[controlled substance]].<ref name="INCB">{{cite web | url = http://www.incb.org/pdf/e/list/green.pdf | title = List of psychotropic substances under international control | location = Viennam, Austria | publisher = International Narcotics Control Board | edition = 23rd | date = August 2003 | quote = Annual Estimates Of Requirements Of Narcotic Drugs, Manufacture Of Synthetic Drugs, Opium Production And Cultivation | archive-url=https://web.archive.org/web/20051205125434/http://www.incb.org/pdf/e/list/green.pdf |archive-date= 5 December 2005 }}</ref> Pemoline is Schedule IV Non-Narcotic (Stimulant) controlled substance with a DEA ACSCN of 1530 and is not subject to annual manufacturing quotas.<ref name="CRC2014" />
==Research==
===Fatigue=== Pemoline has been studied in and reported to be effective in the treatment of [[fatigue (medical)|fatigue]] due to [[multiple sclerosis]] and [[HIV]]-related disease.<ref name="KaminskiSjøgren2007">{{cite journal | vauthors = Kaminski M, Sjøgren P| title=The use of psychostimulants in palliative and supportive treatment of cancer patients | journal=Advances in Palliative Medicine | volume=6 | issue=1 | date=2007-02-22 | issn=1898-3863 | pages=23–32 | url=https://journals.viamedica.pl/advances_in_palliative_medicine/article/view/29461 | language=pl | access-date=2022-05-09}}</ref>
==References== {{Reflist}}
{{Stimulants}} {{ADHD pharmacotherapies}} {{Monoamine releasing agents}}
[[Category:Aminorexes]] [[Category:Drugs developed by AbbVie]] [[Category:Hepatotoxins]] [[Category:Norepinephrine-dopamine releasing agents]] [[Category:Oxazolidinones]] [[Category:Stimulants]] [[Category:Substances discovered in the 1910s]] [[Category:Wakefulness-promoting agents]] [[Category:Withdrawn drugs]] [[Category:Recreational drug metabolites]]