Editing Methylphenidate (section)

{{Short description|Central nervous system stimulant}}
{{Use dmy dates|date=September 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 464371569
| image = Methylphenidate stereoisomers labelled.svg
| image_class = skin-invert-image
| width = 250
| alt = 
| caption = 
| image2 = Methylphenidate-enantiomers-3D-balls.png
| width2 = 250
| alt2 = <!-- Clinical data -->
| pronounce = {{IPAc-en|ˌ|m|ɛ|θ|əl|ˈ|f|ɛ|n|ɪ|d|eɪ|t|,_|-|ˈ|f|iː|-}}
| tradename = Ritalin, Concerta, and others
| Drugs.com = {{drugs.com|monograph|methylphenidate-hydrochloride}}
| MedlinePlus = a682188
| DailyMedID = Methylphenidate
| pregnancy_AU = D
| pregnancy_AU_comment = 
| pregnancy_category = 
| dependency_liability = [[Physical dependence|Physical]]: None<br />[[Psychological dependence|Psychological]]: Moderate<ref name="Stahl's Essential Psychopharmacology">{{cite book | vauthors=Stahl SM | title=Prescriber's Guide: Stahl's Essential Psychopharmacology | date=April 2024 | publisher=Cambridge University Press | location=Cambridge, United Kingdom | isbn=9781108228749 | pages=503–510 | edition=8th | chapter=Methylphenidate (D,L) }}</ref>
| addiction_liability = Moderate <!-- PLEASE NOTE: countless sources state that methylphenidate has a "High" abuse liability. This term is not synonymous with "addiction liability", which is the relative risk (compared to other addictive drugs) of developing an addiction (aka "substance use disorder") when it's used as prescribed or recreationally. -->
| routes_of_administration = [[Oral administration|By mouth]], [[transdermal]], [[Insufflation (medicine)|insufflation]], [[sublingual]], [[Rectal administration|rectal]], [[intravenous]]
<ref name=AHFS2018/>
| class = [[Stimulant]]; [[Norepinephrine–dopamine reuptake inhibitor]] (NDRI)
| ATC_prefix = N06
| ATC_suffix = BA04
| ATC_supplemental = <!-- Legal status -->
| legal_AU = S8
| legal_AU_comment = 
| legal_BR = A3
| 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=3 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = Schedule III
| legal_CA_comment = <ref>{{cite web | title=Ritalin Product information | website=Health Canada | date=25 April 2012 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=800 | access-date=11 June 2022 | archive-date=11 June 2022 | archive-url=https://web.archive.org/web/20220611233512/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=800 | url-status=live }}</ref><ref>{{cite web | title=Controlled Drugs and Substances Act | website=Justice Laws Website | date=31 March 2022 | url=https://laws-lois.justice.gc.ca/eng/acts/C-38.8/FullText.html | access-date=11 June 2022 | archive-date=21 August 2021 | archive-url=https://web.archive.org/web/20210821102842/https://laws-lois.justice.gc.ca/eng/acts/c-38.8/fulltext.html | url-status=live }}</ref><ref>{{cite web | title=Mental health | website=[[Health Canada]] | date=9 May 2018 | url=https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/mental-health.html | access-date=13 April 2024}}</ref>
| legal_DE = Anlage III
| legal_DE_comment = 
| legal_NZ_comment = 
| legal_UK = Class B
| legal_NZ = Class B
| legal_UK_comment = 
| legal_US = Schedule II
| legal_US_comment = <ref name="Finlator_1971">{{cite web | vauthors = Finlator J |date=28 October 1971 |title=Phenmetrazine and its salts, and Methylphenidate |url=https://archives.federalregister.gov/issue_slice/1971/10/28/20685-20687.pd#page=2f|url-status=live |archive-url=https://web.archive.org/web/20241127170445/https://archives.federalregister.gov/issue_slice/1971/10/28/20685-20687.pdf#page=2|archive-date=27 November 2024|access-date=21 December 2024 |website=[[Federal Register]]|publisher=[[Bureau of Narcotics and Dangerous Drugs]]}}</ref>
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Tuzulby EPAR" /><ref name="Tuzulby PI" />
| legal_UN = P II <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->| bioavailability = Insufflation: ~70% 
Oral: ~30% (range: 11–52%)
| protein_bound = 10–33%
| metabolism = [[Liver]] (80%) mostly [[CES1]]-mediated
| metabolites = 
| onset = 
| elimination_half-life = 2–3 hours<ref name="pmid10628897"/>
| duration_of_action = {{ubl
| {{abbr|IR}} dosing: 3–4 hours
| {{abbr|ER}} dosing: 8–12 hours
}}
| excretion = [[Urine]] (90%)

<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 20748-11-2
| CAS_supplemental = 
| PubChem = 4158
| IUPHAR_ligand = 7236
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00422
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4015
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 207ZZ9QZ49
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D04999
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 6887
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 796
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = MPH<ref name="Hodgkins_2012" />

<!-- Chemical and physical data -->| IUPAC_name = Methyl phenyl(piperidin-2-yl)acetate <!-- the locant '2' for acetic acid is not cited -->
| C = 14
| H = 19
| N = 1
| O = 2
| SMILES = COC(=O)C(c1ccccc1)C1CCCCN1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DUGOZIWVEXMGBE-UHFFFAOYSA-N
| density = 
| density_notes = 
| melting_point = 74
| melting_high = 
| melting_notes = <ref name="Pubchem properties">{{cite web|title=Methylphenidate|url=https://pubchem.ncbi.nlm.nih.gov/compound/4158 |website=Pubchem|access-date=4 September 2017|archive-date=6 January 2014|archive-url=https://web.archive.org/web/20140106100442/http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4158#x27|url-status=live}}</ref>
| boiling_point = 136
| boiling_notes = <ref name="Pubchem properties" />
| solubility = 
| sol_units = 
| specific_rotation = 
}}

'''Methylphenidate''', sold under the brand names '''Ritalin''' ({{IPAc-en|ˈ|r|ɪ|t|ə|l|ɪ|n}} {{respell|RIT|ə|lin}}) and '''Concerta''' ({{IPAc-en|k|ə|n|ˈ|s|ɜːr|t|ə}} {{respell|kən|SUR|tə}}) among others, is a [[central nervous system]] (CNS) [[stimulant]] used in the treatment of [[attention deficit hyperactivity disorder]] (ADHD) and [[narcolepsy]]. It may be taken [[Oral administration|by mouth]] or applied to the skin, and different formulations have varying durations of effect.<ref name=AHFS2018>{{cite web |title=Methylphenidate Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/methylphenidate-hydrochloride.html |website=Drugs.com |publisher=AHFS |access-date=19 December 2018 |archive-url=https://web.archive.org/web/20181219182550/https://www.drugs.com/monograph/methylphenidate-hydrochloride.html |archive-date=19 December 2018 |url-status=live }}</ref> For ADHD, the effectiveness of methylphenidate is comparable to [[atomoxetine]]<ref name="Bushe_2016">{{cite journal | vauthors = Bushe C, Day K, Reed V, Karlsdotter K, Berggren L, Pitcher A, Televantou F, Haynes V | title = A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients | journal = Journal of Psychopharmacology | volume = 30 | issue = 5 | pages = 444–458 | date = May 2016 | pmid = 27005307 | doi = 10.1177/0269881116636105 | s2cid = 104938 }}</ref><ref name="Hazell_2011">{{cite journal | vauthors = Hazell PL, Kohn MR, Dickson R, Walton RJ, Granger RE, Wyk GW | title = Core ADHD symptom improvement with atomoxetine versus methylphenidate: a direct comparison meta-analysis | journal = Journal of Attention Disorders | volume = 15 | issue = 8 | pages = 674–683 | date = November 2011 | pmid = 20837981 | doi = 10.1177/1087054710379737 | s2cid = 43503227 }}</ref><ref name="Hanwella_2011">{{cite journal | vauthors = Hanwella R, Senanayake M, de Silva V | title = Comparative efficacy and acceptability of methylphenidate and atomoxetine in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis | journal = BMC Psychiatry | volume = 11 | issue = 1 | pages = 176 | date = November 2011 | pmid = 22074258 | pmc = 3229459 | doi = 10.1186/1471-244X-11-176 | doi-access = free }}</ref><ref name="Rezaei_2016">{{cite journal | vauthors = Rezaei G, Hosseini SA, Akbari Sari A, Olyaeemanesh A, Lotfi MH, Yassini M, Bidaki R, Nouri B | title = Comparative efficacy of methylphenidate and atomoxetine in the treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review and meta-analysis | journal = Medical Journal of the Islamic Republic of Iran | volume = 30 | pages = 325 | date = 10 February 2016 | pmid = 27390695 | pmc = 4898838 }}</ref> but modestly lower than [[amphetamine]]s,<ref>{{cite journal | vauthors = Stuhec M, Lukić P, Locatelli I | title = Efficacy, Acceptability, and Tolerability of Lisdexamfetamine, Mixed Amphetamine Salts, Methylphenidate, and Modafinil in the Treatment of Attention-Deficit Hyperactivity Disorder in Adults: A Systematic Review and Meta-analysis | journal = The Annals of Pharmacotherapy | volume = 53 | issue = 2 | pages = 121–133 | date = February 2019 | pmid = 30117329 | doi = 10.1177/1060028018795703 | s2cid = 52019992 }}</ref><ref>{{cite journal | vauthors = Faraone SV, Pliszka SR, Olvera RL, Skolnik R, Biederman J | title = Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a reanalysis using drug-placebo and drug-drug response curve methodology | journal = Journal of Child and Adolescent Psychopharmacology | volume = 11 | issue = 2 | pages = 171–180 | date = June 2001 | pmid = 11436957 | doi = 10.1089/104454601750284081 | id = {{ProQuest|204600452}} }}</ref><ref>{{cite journal | vauthors = Faraone SV, Biederman J, Roe C | title = Comparative efficacy of Adderall and methylphenidate in attention-deficit/hyperactivity disorder: a meta-analysis | journal = Journal of Clinical Psychopharmacology | volume = 22 | issue = 5 | pages = 468–473 | date = October 2002 | pmid = 12352269 | doi = 10.1097/00004714-200210000-00005 | s2cid = 19726926 }}</ref><ref>{{cite journal | vauthors = Faraone SV, Buitelaar J | title = Comparing the efficacy of stimulants for ADHD in children and adolescents using meta-analysis | journal = European Child & Adolescent Psychiatry | volume = 19 | issue = 4 | pages = 353–364 | date = April 2010 | pmid = 19763664 | doi = 10.1007/s00787-009-0054-3 | s2cid = 9447892 }}</ref> alleviating the [[Executive functions|executive functioning]] deficits of sustained attention, inhibition, working memory, reaction time<ref>{{cite journal | vauthors = Isfandnia F, El Masri S, Radua J, Rubia K | title = The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: A systematic review and meta-analysis | journal = Neuroscience and Biobehavioral Reviews | volume = 162 | pages = 105703 | date = July 2024 | pmid = 38718988 | doi = 10.1016/j.neubiorev.2024.105703 | url = https://kclpure.kcl.ac.uk/portal/en/publications/69dc26fe-1517-438e-9cd7-6788fc396dc9 }}</ref> and emotional self-regulation.<ref>{{cite journal | vauthors = Faraone SV, Banaschewski T, Coghill D, Zheng Y, Biederman J, Bellgrove MA, Newcorn JH, Gignac M, Al Saud NM, Manor I, Rohde LA, Yang L, Cortese S, Almagor D, Stein MA, Albatti TH, Aljoudi HF, Alqahtani MM, Asherson P, Atwoli L, Bölte S, Buitelaar JK, Crunelle CL, Daley D, Dalsgaard S, Döpfner M, Espinet S, Fitzgerald M, Franke B, Gerlach M, Haavik J, Hartman CA, Hartung CM, Hinshaw SP, Hoekstra PJ, Hollis C, Kollins SH, Sandra Kooij JJ, Kuntsi J, Larsson H, Li T, Liu J, Merzon E, Mattingly G, Mattos P, McCarthy S, Mikami AY, Molina BS, Nigg JT, Purper-Ouakil D, Omigbodun OO, Polanczyk GV, Pollak Y, Poulton AS, Rajkumar RP, Reding A, Reif A, Rubia K, Rucklidge J, Romanos M, Ramos-Quiroga JA, Schellekens A, Scheres A, Schoeman R, Schweitzer JB, Shah H, Solanto MV, Sonuga-Barke E, Soutullo C, Steinhausen HC, Swanson JM, Thapar A, Tripp G, van de Glind G, van den Brink W, Van der Oord S, Venter A, Vitiello B, Walitza S, Wang Y | title = The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder | journal = Neuroscience and Biobehavioral Reviews | volume = 128 | pages = 789–818 | date = September 2021 | pmid = 33549739 | pmc = 8328933 | doi = 10.1016/j.neubiorev.2021.01.022 }}</ref><ref>{{cite journal | doi=10.1037/pas0000006 | title=Executive function assessment and adult attention-deficit/Hyperactivity disorder: Tasks versus ratings on the Barkley Deficits in Executive Functioning Scale | date=2014 | journal=Psychological Assessment | volume=26 | issue=4 | pages=1095–1105 | pmid=24885846 | vauthors = Kamradt JM, Ullsperger JM, Nikolas MA }}</ref>

<!-- Side effects -->
Common adverse reactions of methylphenidate include [[euphoria]], [[Mydriasis|dilated pupils]], [[tachycardia]], [[palpitations]], [[headache]], [[insomnia]], [[anxiety]], [[hyperhidrosis]], [[weight loss]], [[Anorexia (symptom)|decreased appetite]], [[Xerostomia|dry mouth]], [[nausea]], and [[abdominal pain]].<ref name="Ritalin FDA label">{{cite web |date=26 June 2021 |title=Ritalin- methylphenidate hydrochloride tablet |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c0bf0835-6a2f-4067-a158-8b86c4b0668a |url-status=live |archive-url=https://web.archive.org/web/20170320052349/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c0bf0835-6a2f-4067-a158-8b86c4b0668a |archive-date=20 March 2017 |access-date=26 March 2022 |website=DailyMed}}</ref> [[Drug withdrawal|Withdrawal symptoms]] may include [[chills]], [[Depression (mood)|depression]], [[drowsiness]], [[dysphoria]], [[fatigue|exhaustion]], [[headache]], [[irritability]], [[lethargy]], [[nightmare]]s, [[Psychomotor agitation|restlessness]], [[Suicidal ideation|suicidal thoughts]], and [[weakness]].<ref name="AHFS2018"/>

<!-- Mechanism of action -->
Methylphenidate is believed to work by blocking the [[reuptake]] of [[dopamine]] and [[norepinephrine]] by [[neuron]]s.<ref name="Arn2005">{{cite journal | vauthors = Arnsten AF, Li BM | title = Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions | journal = Biological Psychiatry | volume = 57 | issue = 11 | pages = 1377–1384 | date = June 2005 | pmid = 15950011 | doi = 10.1016/j.biopsych.2004.08.019 | s2cid = 22992765 }}</ref><ref name="St4th">{{cite book | vauthors = Stahl SM |date=11 April 2013 |title=Stahl's Essential Psychopharmacology: Neuroscientific basis and practical applications |publisher=Cambridge University Press |isbn=978-1-107-68646-5 |edition=4th}}</ref> It is a [[central nervous system]] (CNS) stimulant of the [[substituted phenethylamine|phenethylamine]] and [[piperidine]] classes. It is available as a [[generic medication]].<ref name=AHFS2019>{{cite web |title=Methylphenidate Monograph for Professionals |url=https://www.drugs.com/monograph/methylphenidate.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=2 February 2019 |language=en |archive-date=3 February 2019 |archive-url=https://web.archive.org/web/20190203030724/https://www.drugs.com/monograph/methylphenidate.html |url-status=live }}</ref> In 2022, it was the 32nd most commonly prescribed medication in the United States, with more than 17{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref name="Clincalc Methylphenidate">{{cite web | title = Methylphenidate Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Methylphenidate | access-date = 30 August 2024 }}</ref>

Methylphenidate is under preliminary research for its potential effectiveness in treating apathy in [[Alzheimer's disease|Alzheimer’s disease]], reducing hospitalization rates in [[schizophrenia]], serving as a replacement therapy in stimulant addiction, and improving symptoms of [[social anxiety disorder]] comorbid with ADHD.