Editing Methylphenidate (section)

== Chemistry ==
{{see also|List of methylphenidate analogues}}Despite the claim made by some urban legends, it is not a [[cocaine]] derivative nor analog, however, both compounds contain a methyl piperidinylcarboxylate moiety with 2-[[carbon]] distance between [[nitrogen]] and [[Carboxylate|methanoate]], methylphenidate containing methyl (piperidin-2-yl)-ethanoate and cocaine containing methyl (piperidin-3-yl)-methanoate. Cocaine is a [[local anesthetic]] and ligand channel blocker with [[SNDRI]] action, while methylphenidate is an [[Norepinephrine–dopamine reuptake inhibitor|NDRI]] with 2–3&nbsp;fold selectivity for the [[dopamine transporter]] (DAT) over the [[norepinephrine transporter]] (NET). Cocaine is also more potent in [[serotonin transporter]]s (SERTs) than NDRI sites.<ref>{{cite book |url=https://books.google.com/books?id=Yu9eBwAAQBAJ&pg=PA651 |title=Neuropathology of Drug Addictions and Substance Misuse |vauthors=Preedy VR |date=2016 |publisher=Academic Press |isbn=978-0-12-800677-1 |volume=3: General processes and mechanisms, prescription medications, caffeine and areca, polydrug misuse, emerging addictions, and non-drug addictions |page=651 |access-date=19 December 2018 |archive-url=https://web.archive.org/web/20210829151101/https://books.google.com/books?id=Yu9eBwAAQBAJ&pg=PA651 |archive-date=29 August 2021 |url-status=live}}</ref><ref name="Systematic 2014 - Amph, MPH, Modafinil">{{cite journal |vauthors=Bagot KS, Kaminer Y |date=April 2014 |title=Efficacy of stimulants for cognitive enhancement in non-attention deficit hyperactivity disorder youth: A systematic review |journal=Addiction |volume=109 |issue=4 |pages=547–557 |doi=10.1111/add.12460 |pmc=4471173 |pmid=24749160}}</ref>

Four [[isomer]]s of methylphenidate are possible, since the molecule has two [[chiral centers]]. One pair of [[threo]] isomers and one pair of [[erythro]] are distinguished, from which primarily [[d-threo-methylphenidate]] exhibits the pharmacologically desired effects.<ref name="Heal DJ, Pierce DM 2006 713–38" /><ref>{{cite journal | vauthors = Froimowitz M, Patrick KS, Cody V | title = Conformational analysis of methylphenidate and its structural relationship to other dopamine reuptake blockers such as CFT | journal = Pharmaceutical Research | volume = 12 | issue = 10 | pages = 1430–1434 | date = October 1995 | pmid = 8584475 | doi = 10.1023/A:1016262815984 | s2cid = 26097197 }}</ref> The erythro [[diastereomer]]s are ''[[pressor]]'' amines, a property not shared with the threo diastereomers. When the drug was first introduced it was sold as a 4:1&nbsp;mixture of erythro:threo diastereomers, but it was later reformulated to contain only the threo diastereomers. "TMP" refers to a threo product that does not contain any erythro diastereomers, i.e. (±)-threo-methylphenidate. Since the threo isomers are energetically favored, it is easy to [[epimerize]] out any of the undesired erythro isomers. The drug that contains only [[dextrorotatory]] methylphenidate is sometimes called d-TMP, although this name is only rarely used and it is much more commonly referred to as [[dexmethylphenidate]], d-MPH, or d-threo-methylphenidate. A review on the synthesis of [[enantiopure drug|enantiomerically pure]] (2''R'',2'''R'')-(+)-''threo''-methylphenidate hydrochloride has been published.<ref name="Prashad">{{cite journal | doi =10.1002/1615-4169(200107)343:5<379::AID-ADSC379>3.0.CO;2-4| vauthors = Prashad M | year = 2001 | title = Approaches to the Preparation of Enantiomerically Pure (2R,2{{prime}}R)-(+)-threo-Methylphenidate Hydrochloride | journal = Adv. Synth. Catal. | volume = 343 | issue = 5 | pages = 379–392 }}</ref>

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|image1=Methylphenidate axten.png
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|caption1=Method 1: Methylphenidate preparation elucidated by Axten ''et al.'' (1998)<ref>{{cite journal | doi = 10.1021/jo982214t | title = A Stereoselective Synthesis of dl-threo-Methylphenidate: Preparation and Biological Evaluation of Novel Analogues | year = 1998 |vauthors=Axten JM, Krim L, Kung HF, Winkler JD | journal = The Journal of Organic Chemistry | volume = 63 | issue = 26 | pages = 9628–9629 }}</ref> via [[Bamford–Stevens reaction]].
|alt1=Methylphenidate synthesis graphic

|image2=Methylphenidate classic2.png
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|caption2=Method 2: Classic methylphenidate synthesis<ref name=erowid>{{cite journal | vauthors = Singh S | title = Chemistry, design, and structure-activity relationship of cocaine antagonists | journal = Chemical Reviews | volume = 100 | issue = 3 | pages = 925–1024 | date = March 2000 | pmid = 11749256 | doi = 10.1021/cr9700538 }}</ref>
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=== Detection in biological fluids ===

The concentration of methylphenidate or [[ritalinic acid]], its major [[metabolite]], may be quantified in plasma, serum, or whole blood to monitor compliance in those receiving the drug therapeutically, to confirm the diagnosis of potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage.<ref>{{cite book |veditors=Baselt R |year=2011 |title=Disposition of Toxic Drugs and Chemicals in Man |edition=9th |publisher=Biomedical Publications |place=Seal Beach, CA |pages=1091–1093}}</ref>