Methylphenidate: Difference between revisions

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==History and culture==

Methylphenidate was first licensed by the U.S. Food and Drug Administration (FDA) in 1955 for treating what was then known as "hyperactivity."{{citation needed}} Although it was prescribed to patients as early as 1960, it only became heavily prescribed in the 1990s when the diagnosis of ADHD itself became more widely accepted.<ref>{{cite book | vauthors=((Diller, L. H.)) | date= 1999 | title=Running on ritalin: a physician reflects on children, society, and performance in a pill | publisher=Bantam Books | isbn=9780553379068}}</ref><ref>{{cite journal | vauthors=((Lange, K. W.)), ((Reichl, S.)), ((Lange, K. M.)), ((Tucha, L.)), ((Tucha, O.)) | journal=Attention Deficit and Hyperactivity Disorders | title=The history of attention deficit hyperactivity disorder | volume=2 | issue=4 | pages=241–255 | date= 2010 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000907/ | issn=1866-6116 | doi=10.1007/s12402-010-0045-8}}</ref>

The compound was first synthesized in 1944 by chemist Leandro Panizzon and marketed as “Ritalin” by Swiss company CIBA (now Novartis) in 1954. The name “Ritalin” derives from the first name of Panizzon’s wife, i.e. Marguerite, nicknamed Rita,<ref>https://pmc.ncbi.nlm.nih.gov/articles/PMC3000907/#Sec8</ref> who used Ritalin to compensate for low blood pressure.<ref>Richard L. Myers https://books.google.com/books?id=a4DuGVwyN6cC&q=named+ritalin+after+his+wife&pg=PA178 ABC-CLIO. p. 178. ISBN 978-0-313-33758-1.</ref>

It was estimated that the number of doses of methylphenidate used globally in 2013 increased by 66% compared to 2012.<ref>{{cite journal | journal=The Pharmaceutical Journal | title=Narcotics monitoring board reports 66% increase in global consumption of methylphenidate | date= 2015 | url=http://www.pharmaceutical-journal.com/news-and-analysis/news-in-brief/narcotics-monitoring-board-reports-66-increase-in-global-consumption-of-methylphenidate/20068042.article | issn=2053-6186 | doi=10.1211/PJ.2015.20068042}}</ref> In 2019, it was the 51st most commonly prescribed medication in the United States, with more than 14 million prescriptions.<ref>{{cite web |title=The Top 300 of 2019 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |website=ClinCalc |access-date=16 October 2021 }}</ref><ref>{{cite web | title=Methylphenidate - Drug Usage Statistics | website=ClinCalc | url=https://clincalc.com/DrugStats/Drugs/Methylphenidate | access-date=16 October 2021}}</ref> It is available as a generic medication.

Methylphenidate was not reported to be a stimulant until 1954.<ref>Heal DJ, Pierce DM (2006). "Methylphenidate and its isomers: their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system". ''CNS Drugs''. '''20''' (9): 713–738. doi:[https://link.springer.com/article/10.2165/00023210-200620090-00002 10.2165/00023210-200620090-00002]. [https://pubmed.ncbi.nlm.nih.gov/16953648/ PMID 16953648.] [https://www.semanticscholar.org/paper/Methylphenidate-and-its-Isomers-Heal-Pierce/b19872ac87ae24e3cd161a1719d192b9fccffa1b S2CID 39535277.]</ref> The drug was introduced for medical use in the United States in 1957.<ref>Wood S, Sage JR, Shuman T, Anagnostaras SG (2014). "Psychostimulants and cognition: A continuum of behavioral and cognitive activation". ''Pharmacol Rev''. '''66''' (1): 193–221. https://pmc.ncbi.nlm.nih.gov/articles/PMC3880463/</ref> Although it was first used to allay [[Barbiturates|barbiturate]]-induced coma, narcolepsy, and depression.<ref>Myers RL (August 2007). [https://archive.org/details/100mostimportant0000myer ''The 100 Most Important Chemical Compounds: A reference guide''.] ABC-CLIO. p. 178. [[ISBN (identifier)|ISBN]] [[Special:BookSources/978-0-313-33758-1|<bdi>978-0-313-33758-1</bdi>]].</ref> It was later used to treat memory deficits in the elderly.<ref>Stolerman I (2010). ''Encyclopedia of Psychopharmacology''. Berlin, DE / London, UK: Springer. p. 763. ISBN [[Special:BookSources/978-3-540-68698-9|<bdi>978-3-540-68698-9</bdi>]].</ref> Production and prescription only rose significantly in the 1990s, especially in the United States, as the ADHD diagnosis came to be better understood and more generally accepted within the medical and mental health communities.<ref>Woodworth T (16 May 2000). [https://web.archive.org/web/20071012061712/http://www.dea.gov/pubs/cngrtest/ct051600.htm DEA Congressional Testimony (Report)]. U.S. Drug Enforcement Administration. Archived from [https://www.dea.gov/pubs/cngrtest/ct051600.htm the original] on 12 October 2007. Retrieved 2 November 2007.</ref>

In 2000, Alza Corporation received US FDA approval to market Concerta, an extended-release form of methylphenidate.<ref>[https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a88218c-5b18-4220-8f56-526de1a276cd "Concerta- methylphenidate hydrochloride tablet, extended release"]. ''DailyMed''. 1 July 2021.</ref><ref>[https://web.archive.org/web/20101216171133/http://centerwatch.com/drug-information/fda-approvals/drug-details.aspx?DrugID=637 "Newly Approved Drug Therapies (637) Concerta, Alza".] ''CenterWatch''. Archived from [https://www.centerwatch.com/drug-information/fda-approvals/drug-details.aspx?DrugID=637 the original] on 16 December 2010. Retrieved 30 April 2011.</ref>

It was estimated that the number of doses of methylphenidate used globally in 2013 increased by 66% compared to 2012.<ref>{{cite journal | journal=The Pharmaceutical Journal | title=Narcotics monitoring board reports 66% increase in global consumption of methylphenidate | date= 2015 | url=http://www.pharmaceutical-journal.com/news-and-analysis/news-in-brief/narcotics-monitoring-board-reports-66-increase-in-global-consumption-of-methylphenidate/20068042.article | issn=2053-6186 | doi=10.1211/PJ.2015.20068042}}</ref> In ~~2022~~, it was the ~~32nd~~ most commonly prescribed medication in the United States, with more than 17 million prescriptions.<ref>[https://clincalc.com/DrugStats/~~Drugs/Methylphenidate "Methylphenidate Drug Usage Statistics, United States, 2013 - 2022"]~~. ''ClinCalc~~''. Retrieved 30 August 2024.~~</ref> ~~It is available as a generic medication.~~<ref>[https://~~www.drugs~~.com/~~monograph~~/~~methylphenidate.html "Methylphenidate Hydrochloride Monograph for Professionals".] ''~~Drugs~~.com''. AHFS. Archived from [https:~~/~~/web.archive.org/web/20181003194029/https://www.drugs.com/monograph/methylphenidate~~-~~hydrochloride.html the original] on 19 December 2018. Retrieved 19 December 2018.~~</ref>

==Chemistry==

Methylphenidate is a synthetic molecule of the [[substituted phenethylamine]] and [[substituted phenidate]] classes. It contains a phenethylamine core featuring a phenyl ring bound to an amino (-NH2) group through an ethyl chain.

It is structurally similar to [[amphetamine]], featuring a substitution at Rα which is incorporated into a [[piperidine]] ring ending at the terminal amine of the phenethylamine chain. Additionally, it contains a methyl ~~acetate~~ bound to Rβ of its structure.

It is structurally similar to [[amphetamine]], featuring a substitution at Rα which is incorporated into a [[piperidine]] ring ending at the terminal amine of the phenethylamine chain. Additionally, it contains a methyl carboxylate bound to Rβ of its structure.

===Dexmethylphenidate===

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*'''Austria''': Methylphenidate is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).{{citation needed}}

*'''Canada''': Methylphenidate is listed in Schedule III of the Controlled Drugs and Substances Act (along with LSD, psychedelic mushrooms, and mescaline).<ref>{{cite web|url=http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-32.html#h-28|title=SCHEDULE III|publisher=Department of Justice|access-date=December 24, 2019|archive-url=https://web.archive.org/web/20110416090043/http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-32.html#h-28|archive-date=April 16, 2011}}</ref> It is illegal to possess without a prescription pursuant to Part G (section G.01.002) of the Food and Drug Regulations under the Food and Drugs Act.

*'''France''': Methylphenidate is scheduled as a "stupéfiant", i.e. a recognized drug of abuse. It can only be prescribed on a narcotic prescription form.<ref>{{Citation | title=Arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants | url=https://www.legifrance.gouv.fr/loda/id/JORFTEXT000000533085/2020-11-20/}}</ref>

*'''Germany''': Methylphenidate is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.<ref>{{Citation | title=Anlage III BtMG - Einzelnorm | url=http://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html}}</ref>

*'''New Zealand''': Methylphenidate is a 'Class B2 controlled substance'. Unlawful possession is punishable by six-month prison sentence and the distribution of it is punishable by a 14-year sentence.{{citation needed}}

*'''Sweden''': Methylphenidate is a List II controlled substance with recognized medical value. Possession without a prescription is punishable by up to three years in prison.<ref>{{Citation | title=Narkotikastrafflag (1968:64) (NSL), Lagen.nu | url=https://lagen.nu/1968:64}}</ref>

*'''Switzerland''': Methylphenidate is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>

*'''Turkey''': Methylphenidate is a 'red prescription' only substance<ref>https://www.titck.gov.tr/~~dinamikmodul~~/43</ref> and illegal when sold or possessed without a prescription.{{citation needed}}

*'''Turkey''': Methylphenidate is a 'red prescription' only substance<ref>KIRMIZI REÇETEYE TABİ İLAÇLAR | https://www.titck.gov.tr/storage/Archive/2019/contentFile/K%C4%B1rm%C4%B1z%C4%B1%20Re%C3%A7eteye%20Tabi%20%C4%B0la%C3%A7lar%2005072019_ebcc7e92-6661-4983-870a-fe8983a9c2b7.pdf</ref> and illegal when sold or possessed without a prescription.{{citation needed}}

*'''United Kingdom''': Methylphenidate is a controlled 'Class B' substance. Possession without a prescription carries with it a sentence of up to 5 years and/or an unlimited fine and supplying it is 14 years and/or an unlimited fine.<ref>{{Citation | title=Misuse of Drugs Act 1971 | url=https://www.legislation.gov.uk/ukpga/1971/38/schedule/2}}</ref>

*'''United States''': Methylphenidate is classified as a Schedule II controlled substance, the designation used for substances that have a recognized medical value but present a high potential for abuse.{{citation needed}}

@@ Line 10: / Line 10: @@
 ==History and culture==
+{{historyStub}}
+Methylphenidate was first licensed by the U.S. Food and Drug Administration (FDA) in 1955 for treating what was then known as "hyperactivity."{{citation needed}} Although it was prescribed to patients as early as 1960, it only became heavily prescribed in the 1990s when the diagnosis of ADHD itself became more widely accepted.<ref>{{cite book | vauthors=((Diller, L. H.)) | date= 1999 | title=Running on ritalin: a physician reflects on children, society, and performance in a pill | publisher=Bantam Books | isbn=9780553379068}}</ref><ref>{{cite journal | vauthors=((Lange, K. W.)), ((Reichl, S.)), ((Lange, K. M.)), ((Tucha, L.)), ((Tucha, O.)) | journal=Attention Deficit and Hyperactivity Disorders | title=The history of attention deficit hyperactivity disorder | volume=2 | issue=4 | pages=241–255 | date= 2010 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000907/ | issn=1866-6116 | doi=10.1007/s12402-010-0045-8}}</ref>
-The compound was first synthesized in 1944 by chemist Leandro Panizzon and marketed as “Ritalin” by Swiss company CIBA (now Novartis) in 1954. The name “Ritalin” derives from the first name of Panizzon’s wife, i.e. Marguerite, nicknamed Rita,<ref>https://pmc.ncbi.nlm.nih.gov/articles/PMC3000907/#Sec8</ref> who used Ritalin to compensate for low blood pressure.<ref>Richard L. Myers https://books.google.com/books?id=a4DuGVwyN6cC&q=named+ritalin+after+his+wife&pg=PA178 ABC-CLIO. p. 178. ISBN 978-0-313-33758-1.</ref>
+It was estimated that the number of doses of methylphenidate used globally in 2013 increased by 66% compared to 2012.<ref>{{cite journal | journal=The Pharmaceutical Journal | title=Narcotics monitoring board reports 66% increase in global consumption of methylphenidate | date= 2015 | url=http://www.pharmaceutical-journal.com/news-and-analysis/news-in-brief/narcotics-monitoring-board-reports-66-increase-in-global-consumption-of-methylphenidate/20068042.article | issn=2053-6186 | doi=10.1211/PJ.2015.20068042}}</ref> In 2019, it was the 51st most commonly prescribed medication in the United States, with more than 14 million prescriptions.<ref>{{cite web |title=The Top 300 of 2019 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |website=ClinCalc |access-date=16 October 2021 }}</ref><ref>{{cite web | title=Methylphenidate - Drug Usage Statistics | website=ClinCalc | url=https://clincalc.com/DrugStats/Drugs/Methylphenidate | access-date=16 October 2021}}</ref> It is available as a generic medication.
-Methylphenidate was not reported to be a stimulant until 1954.<ref>Heal DJ, Pierce DM (2006). "Methylphenidate and its isomers: their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system". ''CNS Drugs''. '''20''' (9): 713–738. doi:[https://link.springer.com/article/10.2165/00023210-200620090-00002 10.2165/00023210-200620090-00002]. [https://pubmed.ncbi.nlm.nih.gov/16953648/ PMID 16953648.] [https://www.semanticscholar.org/paper/Methylphenidate-and-its-Isomers-Heal-Pierce/b19872ac87ae24e3cd161a1719d192b9fccffa1b S2CID 39535277.]</ref> The drug was introduced for medical use in the United States in 1957.<ref>Wood S, Sage JR, Shuman T, Anagnostaras SG (2014). "Psychostimulants and cognition: A continuum of behavioral and cognitive activation". ''Pharmacol Rev''. '''66''' (1): 193–221. https://pmc.ncbi.nlm.nih.gov/articles/PMC3880463/</ref> Although it was first used to allay [[Barbiturates|barbiturate]]-induced coma, narcolepsy, and depression.<ref>Myers RL (August 2007). [https://archive.org/details/100mostimportant0000myer ''The 100 Most Important Chemical Compounds: A reference guide''.] ABC-CLIO. p. 178. [[ISBN (identifier)|ISBN]] [[Special:BookSources/978-0-313-33758-1|<bdi>978-0-313-33758-1</bdi>]].</ref> It was later used to treat memory deficits in the elderly.<ref>Stolerman I (2010). ''Encyclopedia of Psychopharmacology''. Berlin, DE / London, UK: Springer. p. 763. ISBN [[Special:BookSources/978-3-540-68698-9|<bdi>978-3-540-68698-9</bdi>]].</ref> Production and prescription only rose significantly in the 1990s, especially in the United States, as the ADHD diagnosis came to be better understood and more generally accepted within the medical and mental health communities.<ref>Woodworth T (16 May 2000). [https://web.archive.org/web/20071012061712/http://www.dea.gov/pubs/cngrtest/ct051600.htm DEA Congressional Testimony (Report)]. U.S. Drug Enforcement Administration. Archived from [https://www.dea.gov/pubs/cngrtest/ct051600.htm the original] on 12 October 2007. Retrieved 2 November 2007.</ref>
-In 2000, Alza Corporation received US FDA approval to market Concerta, an extended-release form of methylphenidate.<ref>[https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a88218c-5b18-4220-8f56-526de1a276cd "Concerta- methylphenidate hydrochloride tablet, extended release"]. ''DailyMed''. 1 July 2021.</ref><ref>[https://web.archive.org/web/20101216171133/http://centerwatch.com/drug-information/fda-approvals/drug-details.aspx?DrugID=637 "Newly Approved Drug Therapies (637) Concerta, Alza".] ''CenterWatch''. Archived from [https://www.centerwatch.com/drug-information/fda-approvals/drug-details.aspx?DrugID=637 the original] on 16 December 2010. Retrieved 30 April 2011.</ref>
-It was estimated that the number of doses of methylphenidate used globally in 2013 increased by 66% compared to 2012.<ref>{{cite journal | journal=The Pharmaceutical Journal | title=Narcotics monitoring board reports 66% increase in global consumption of methylphenidate | date= 2015 | url=http://www.pharmaceutical-journal.com/news-and-analysis/news-in-brief/narcotics-monitoring-board-reports-66-increase-in-global-consumption-of-methylphenidate/20068042.article | issn=2053-6186 | doi=10.1211/PJ.2015.20068042}}</ref> In 2022, it was the 32nd most commonly prescribed medication in the United States, with more than 17 million prescriptions.<ref>[https://clincalc.com/DrugStats/Drugs/Methylphenidate "Methylphenidate Drug Usage Statistics, United States, 2013 - 2022"]. ''ClinCalc''. Retrieved 30 August 2024.</ref> It is available as a generic medication.<ref>[https://www.drugs.com/monograph/methylphenidate.html "Methylphenidate Hydrochloride Monograph for Professionals".] ''Drugs.com''. AHFS. Archived from [https://web.archive.org/web/20181003194029/https://www.drugs.com/monograph/methylphenidate-hydrochloride.html the original] on 19 December 2018. Retrieved 19 December 2018.</ref>
 ==Chemistry==
 Methylphenidate is a synthetic molecule of the [[substituted phenethylamine]] and [[substituted phenidate]] classes. It contains a phenethylamine core featuring a phenyl ring bound to an amino (-NH<sub>2</sub>) group through an ethyl chain.
-It is structurally similar to [[amphetamine]], featuring a substitution at R<sub>α</sub> which is incorporated into a [[piperidine]] ring ending at the terminal amine of the phenethylamine chain. Additionally, it contains a methyl acetate bound to R<sub>β</sub> of its structure.
+It is structurally similar to [[amphetamine]], featuring a substitution at R<sub>α</sub> which is incorporated into a [[piperidine]] ring ending at the terminal amine of the phenethylamine chain. Additionally, it contains a methyl carboxylate bound to R<sub>β</sub> of its structure.
 ===Dexmethylphenidate===
@@ Line 164: / Line 160: @@
 *'''Austria''': Methylphenidate is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).{{citation needed}}
 *'''Canada''': Methylphenidate is listed in Schedule III of the Controlled Drugs and Substances Act (along with LSD, psychedelic mushrooms, and mescaline).<ref>{{cite web|url=http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-32.html#h-28|title=SCHEDULE III|publisher=Department of Justice|access-date=December 24, 2019|archive-url=https://web.archive.org/web/20110416090043/http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-32.html#h-28|archive-date=April 16, 2011}}</ref> It is illegal to possess without a prescription pursuant to Part G (section G.01.002) of the Food and Drug Regulations under the Food and Drugs Act.
-*'''France''': Methylphenidate is scheduled as a "stupéfiant", i.e. a recognized drug of abuse. It can only be prescribed on a narcotic prescription form.<ref>{{Citation | title=Arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants | url=https://www.legifrance.gouv.fr/loda/id/JORFTEXT000000533085/2020-11-20/}}</ref>
 *'''Germany''': Methylphenidate is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.<ref>{{Citation | title=Anlage III BtMG - Einzelnorm | url=http://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html}}</ref>
 *'''New Zealand''': Methylphenidate is a 'Class B2 controlled substance'. Unlawful possession is punishable by six-month prison sentence and the distribution of it is punishable by a 14-year sentence.{{citation needed}}
 *'''Sweden''': Methylphenidate is a List II controlled substance with recognized medical value. Possession without a prescription is punishable by up to three years in prison.<ref>{{Citation | title=Narkotikastrafflag (1968:64) (NSL), Lagen.nu | url=https://lagen.nu/1968:64}}</ref>
 *'''Switzerland''': Methylphenidate is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
-*'''Turkey''': Methylphenidate is a 'red prescription' only substance<ref>https://www.titck.gov.tr/dinamikmodul/43</ref> and illegal when sold or possessed without a prescription.{{citation needed}}
+*'''Turkey''': Methylphenidate is a 'red prescription' only substance<ref>KIRMIZI REÇETEYE TABİ İLAÇLAR | https://www.titck.gov.tr/storage/Archive/2019/contentFile/K%C4%B1rm%C4%B1z%C4%B1%20Re%C3%A7eteye%20Tabi%20%C4%B0la%C3%A7lar%2005072019_ebcc7e92-6661-4983-870a-fe8983a9c2b7.pdf</ref> and illegal when sold or possessed without a prescription.{{citation needed}}
 *'''United Kingdom''': Methylphenidate is a controlled 'Class B' substance. Possession without a prescription carries with it a sentence of up to 5 years and/or an unlimited fine and supplying it is 14 years and/or an unlimited fine.<ref>{{Citation | title=Misuse of Drugs Act 1971 | url=https://www.legislation.gov.uk/ukpga/1971/38/schedule/2}}</ref>
 *'''United States''': Methylphenidate is classified as a Schedule II controlled substance, the designation used for substances that have a recognized medical value but present a high potential for abuse.{{citation needed}}