Dexmethylphenidate

{{Short description|Central nervous system stimulant}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Use dmy dates|date=October 2022}}

{{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 460779887 | image = Dexmethylphenidate structure.svg | image_class = skin-invert-image | width = 200 | alt = | image2 = Dextromethylphenidate-based-on-hydrochloride-xtal-1995-3D-balls.png | image_class2 = bg-transparent | alt2 =

| tradename = Focalin, Focalin XR, others | Drugs.com = {{drugs.com|monograph|dexmethylphenidate-hydrochloride}} | MedlinePlus = a603014 | DailyMedID = Dexmethylphenidate | pregnancy_AU =  | pregnancy_AU_comment = | pregnancy_category = | dependency_liability = Physical: None Psychological: Moderate<ref name="Stahl's Essential Psychopharmacology">{{cite book | vauthors = Stahl SM | chapter = Methylphenidate (D,L) | title = Prescriber's Guide: Stahl's Essential Psychopharmacology | location = Cambridge, United Kingdom | pages = 503–510 | date = April 2024 | publisher = Cambridge University Press | isbn = 978-1-108-22874-9 | edition = 8th }}</ref> | addiction_liability = Moderate  | routes_of_administration = By mouth | ATC_prefix = N06 | ATC_suffix = BA11 | ATC_supplemental =

| index2_label = hydrochloride | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 40431-64-9 | CAS_number2 = 19262-68-1 | PubChem = 154101 | PubChem2 = 154100 | IUPHAR_ligand = 7554 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB06701 | DrugBank2 = DBSALT001458 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 135807 | ChemSpiderID2 = 135806 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = M32RH9MFGP | UNII2 = 1678OK0E08 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D07806 | KEGG2_Ref = {{keggcite|correct|kegg}} | KEGG2 = D03721 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 51860 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 827 | ChEMBL2 = 904 | synonyms = (2''R'',2′''R'')–(+)–methylphenidate, (α''R'',2''R'')–(+)–methylphenidate,<ref name="Future-Med-Chem-2025">{{cite journal | vauthors = Agranat I, D'Acquarica I | title = Consecutive double chiral-switches strategy. ADHD methylphenidate drugs: from two racemates via racemate to enantiomer | journal = Future Medicinal Chemistry | volume = 17 | issue = 20 | pages = 2493–2510 | date = October 2025 | pmid = 41065534 | pmc = 12536773 | doi = 10.1080/17568919.2025.2561463 | ref = Future-Med-Chem-2025 | pmc-embargo-date = October 9, 2026 }}</ref> d-threo-methylphenidate (d-TMP), d-methylphenidate (d-MPH)

| IUPAC_name = (''R'',''R'')-(+)-Methyl 2-phenyl-2-(2-piperidyl)acetate | C=14 | H=19 | N=1 | O=2 | SMILES = O=C([C@@H]([C@@H]1NCCCC1)C2=CC=CC=C2)OC | SMILES2 = Cl.[H][C@@](C(=O)OC)(C1=CC=CC=C1)[C@@]1([H])CCCCN1 | 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/t12-,13-/m1/s1 | StdInChI2 = 1S/C14H19NO2.ClH/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;1H/t12-,13-;/m1./s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = DUGOZIWVEXMGBE-CHWSQXEVSA-N | StdInChIKey2 = JUMYIBMBTDDLNG-OJERSXHUSA-N }}

'''Dexmethylphenidate''', sold under the brand name '''Focalin''' among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) in those over the age of five years.<ref name="AHFS2019">{{cite web | title = Dexmethylphenidate Hydrochloride Monograph for Professionals | url = https://www.drugs.com/monograph/dexmethylphenidate-hydrochloride.html | website = Drugs.com | publisher = American Society of Health-System Pharmacists | access-date = 15 April 2019 }}</ref> It is taken by mouth.<ref name="AHFS2019" /> The immediate-release formulation lasts up to five hours while the extended-release formulation lasts up to twelve hours.<ref>{{cite book | title = Mosby's Drug Reference for Health Professions - E-Book | pages = 455 | date = 2013 | publisher = Elsevier Health Sciences | isbn = 978-0-323-18760-2 | url = https://books.google.com/books?id=41z07XtCfa0C&pg=PA455 }}</ref> It is the more active enantiomer of methylphenidate.<ref name="AHFS2019" /> Methylphenidate has been shown to be more effective than atomoxetine and superior in treating ADHD symptoms when compared.<ref>{{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 | date = 2011-11-10 | article-number = 176 | doi = 10.1186/1471-244x-11-176 | pmid = 22074258 | doi-access = free | issn = 1471-244X | pmc = 3229459 }}</ref>

Common side effects include abdominal pain, loss of appetite, and fever.<ref name="AHFS2019" /> Serious side effects may include psychosis, sudden cardiac death, mania, anaphylaxis, seizures, and priapism.<ref name="AHFS2019" /> Safety during pregnancy and breastfeeding is unclear.<ref name=Preg2019>{{cite web | title = Dexmethylphenidate Use During Pregnancy | url = https://www.drugs.com/pregnancy/dexmethylphenidate.html | website = Drugs.com | access-date = 15 April 2019 }}</ref>

Dexmethylphenidate was approved for medical use in the United States in 2001.<ref name="Focalin FDA label">{{cite web | title = Focalin- dexmethylphenidate hydrochloride tablet | date = 24 June 2020 | website = DailyMed | url = https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c552f11-e24a-4d9b-bb8d-be10c928eca8 | access-date = 15 November 2020 }}</ref> It is available as a generic medication.<ref name="AHFS2019" /> In 2023, it was the 127th most commonly prescribed medication in the United States, with more than 4{{nbsp}}million prescriptions.<ref name="Top 300">{{cite web | title = Top 300 of 2023 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 12 August 2025 | archive-date = 12 August 2025 | archive-url = https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status = live }}</ref><ref>{{cite web | title = Dexmethylphenidate Drug Usage Statistics, United States, 2014 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Dexmethylphenidate | access-date = 18 August 2025 }}</ref> {{TOC limit}}

==Medical uses== Dexmethylphenidate is used as a treatment for attention deficit hyperactivity disorder (ADHD), usually along with psychological, educational, behavioral or other forms of treatment. It is proposed that stimulants help ameliorate the symptoms of ADHD by making it easier for the user to concentrate, avoid distraction, and control behavior. Placebo-controlled trials have shown that once-daily dexmethylphenidate XR was effective and generally well tolerated.<ref name="Moen_2009">{{cite journal | vauthors = Moen MD, Keam SJ | title = Dexmethylphenidate extended release: a review of its use in the treatment of attention-deficit hyperactivity disorder | journal = CNS Drugs | volume = 23 | issue = 12 | pages = 1057–1083 | date = December 2009 | pmid = 19958043 | doi = 10.2165/11201140-000000000-00000 | s2cid = 24975170 }}</ref>

Improvements in ADHD symptoms in children were significantly greater for dexmethylphenidate XR versus placebo.<ref name="Moen_2009" /> It also showed greater efficacy than osmotic controlled-release oral delivery system (OROS) methylphenidate over the first half of the laboratory classroom day but assessments late in the day favoured OROS methylphenidate.<ref name="Moen_2009" />

==Contraindications== {{transcluded section|source=Methylphenidate}} {{trim|{{#section-h:Methylphenidate|Contraindications}}}}

=== Hypertension === Patients with preexisting high blood pressure or hypertension are at an increased risk of having symptoms worsen due to the use of CNS stimulants.<ref>{{Cite web |title=Dexmethylphenidate Disease Interactions |url=https://www.drugs.com/disease-interactions/dexmethylphenidate.html |access-date=2025-11-23 |website=Drugs.com |language=en}}</ref>

=== Cardiac disease === Sudden death has been reported in patients taking CNS stimulants with cardiac structural abnormalities, arrhythmias, coronary disease, or other forms of cardiac disease. Careful assessment and adjustments to dosage are recommended.

=== Glaucoma === Dexmethylphenidate can increase intraocular pressure(IOP) due to dilation of the pupils. In patients with preexisting glaucoma, IOP can cause further damage to the optic nerve.<ref>{{Cite web |title=Dexmethylphenidate Disease Interactions |url=https://www.drugs.com/disease-interactions/dexmethylphenidate.html |access-date=2025-11-23 |website=Drugs.com |language=en}}</ref>

==Adverse effects== {{transcluded section|source=Methylphenidate|part=yes}} Products containing dexmethylphenidate have a side effect profile comparable to those containing methylphenidate.<ref name="Dexmethylphenidate">{{cite journal | vauthors = Keating GM, Figgitt DP | title = Dexmethylphenidate | journal = Drugs | volume = 62 | issue = 13 | pages = 1899–904; discussion 1905–8 | year = 2002 | pmid = 12215063 | doi = 10.2165/00003495-200262130-00009 | s2cid = 249894173 }}</ref> {{trim|{{#section-h:Methylphenidate|Adverse effects}}}}

== Interactions == {{transcluded section|source=Methylphenidate}} Methylphenidate (MPH) is widely described in the pharmacological literature as being metabolized primarily, and almost exclusively, by carboxylesterase 1 into its inactive metabolite, ritalinic acid (RA). However, enzyme-induction and inhibition data, together with structural biochemical analyses of MPH and related analogues, challenge this CES1-only framework. Accumulating evidence strongly indicates that CYP2B6, CYP2E1, and CYP3A4 contribute substantially to the clearance and metabolic fate of methylphenidate.

Studies examining CYP2B6 show that induction by agents such as carbamazepine produces a marked reduction in circulating methylphenidate concentrations, whereas inhibition—including reports involving turmeric constituents—results in elevated plasma levels and a prolonged duration of action. CYP2E1 has been shown to catalyse α-hydroxylation of the methylphenidate ester side chain, a reaction that promotes its spontaneous degradation to ritalinic acid; inhibition of this isoenzyme, most notably by alcohol, correspondingly increases methylphenidate exposure. CYP3A4 also plays a clinically relevant role, particularly in the presence of ethanol, wherein it mediates the transesterification of methylphenidate to ethylphenidate, an active metabolite. Induction of CYP3A4, including observations associated with glucose-stimulated pathways, increases metabolic flux through this route and can alter drug levels while shortening the duration of effect.

Taken together, these findings indicate that the classical view of methylphenidate metabolism as governed solely by CES1 is incomplete. A multi-enzyme model better accounts for observed clinical pharmacokinetics and drug–drug interactions, with CYP2B6 serving as a major clearance pathway, CYP2E1 generating ritalinic acid through α-hydroxylation, and CYP3A4 producing ethylphenidate in ethanol-containing conditions. {{trim|{{#section-h:Methylphenidate|Interactions}}}}

== Pharmacology== {{main|Methylphenidate#Pharmacology}}

=== Pharmacokinetics === Dexmethylphenidate has a 4–6 hour duration of effect. A long-acting formulation, Focalin XR, which spans 12 hours is also available and has been shown to be as effective as DL (dextro-, levo-)-TMP (threo-methylphenidate) XR (extended release) (Concerta, Ritalin LA), with flexible dosing and good tolerability.<ref>{{cite journal | vauthors = McGough JJ, Pataki CS, Suddath R | title = Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder | journal = Expert Review of Neurotherapeutics | volume = 5 | issue = 4 | pages = 437–441 | date = July 2005 | pmid = 16026226 | doi = 10.1586/14737175.5.4.437 | s2cid = 6561452 }}</ref><ref>{{cite journal | vauthors = Silva R, Tilker HA, Cecil JT, Kowalik S, Khetani V, Faleck H, Patin J | title = Open-label study of dexmethylphenidate hydrochloride in children and adolescents with attention deficit hyperactivity disorder | journal = Journal of Child and Adolescent Psychopharmacology | volume = 14 | issue = 4 | pages = 555–563 | year = 2004 | pmid = 15662147 | doi = 10.1089/cap.2004.14.555 }}</ref> It has also been demonstrated to reduce ADHD symptoms in both children<ref>{{cite journal | vauthors = Arnold LE, Lindsay RL, Conners CK, Wigal SB, Levine AJ, Johnson DE, West SA, Sangal RB, Bohan TP, Zeldis JB | title = A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder | journal = Journal of Child and Adolescent Psychopharmacology | volume = 14 | issue = 4 | pages = 542–554 | date = Winter 2004 | pmid = 15662146 | doi = 10.1089/cap.2004.14.542 | hdl = 1811/51584 | hdl-access = free }}</ref> and adults.<ref>{{cite journal | vauthors = Spencer TJ, Adler LA, McGough JJ, Muniz R, Jiang H, Pestreich L | title = Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder | journal = Biological Psychiatry | volume = 61 | issue = 12 | pages = 1380–1387 | date = June 2007 | pmid = 17137560 | doi = 10.1016/j.biopsych.2006.07.032 | s2cid = 45976373 | doi-access = free }}</ref> d-MPH has a similar side-effect profile to MPH<ref name="Dexmethylphenidate" /> and can be administered without regard to food intake.<ref>{{cite journal | vauthors = Teo SK, Scheffler MR, Wu A, Stirling DI, Thomas SD, Stypinski D, Khetani VD | title = A single-dose, two-way crossover, bioequivalence study of dexmethylphenidate HCl with and without food in healthy subjects | journal = Journal of Clinical Pharmacology | volume = 44 | issue = 2 | pages = 173–178 | date = February 2004 | pmid = 14747426 | doi = 10.1177/0091270003261899 | s2cid = 20694072 }}</ref>

'''CTx-1301''' is an experimental medication that is an extended-release formulation of dexmethylphenidate that has a half life more than an hour longer than extended-release dexmethylphenidate (d-MPH-ER). It is under development for ADHD.<ref>{{cite journal | vauthors = Brady LS, Lisanby SH, Gordon JA | title = New directions in psychiatric drug development: promising therapeutics in the pipeline | journal = Expert Opinion on Drug Discovery | volume = 18 | issue = 8 | pages = 835–850 | date = 3 August 2023 | pmid = 37352473 | doi = 10.1080/17460441.2023.2224555 | s2cid = 259240509 }}</ref><ref>{{cite journal | vauthors = Childress AC, Beltran N, Supnet C, Weiss MD | title = Reviewing the role of emerging therapies in the ADHD armamentarium | journal = Expert Opinion on Emerging Drugs | volume = 26 | issue = 1 | pages = 1–16 | date = March 2021 | pmid = 33143485 | doi = 10.1080/14728214.2020.1846718 | s2cid = 226251694 }}</ref><ref>{{cite journal | vauthors = Ryst E, Childress A | title = An updated safety review of the current drugs for managing ADHD in children | journal = Expert Opinion on Drug Safety | volume = 22 | issue = 11 | pages = 1025–1040 | date = 2023 | pmid = 37843488 | doi = 10.1080/14740338.2023.2271392 | s2cid = 264144450 }}</ref><ref>{{cite journal | vauthors = Harris E | title = Industry update: what is new in the field of therapeutic delivery? | journal = Therapeutic Delivery | volume = 9 | issue = 3 | pages = 155–161 | date = 1 February 2018 | doi = 10.4155/tde-2017-0117 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Childress AC, Komolova M, Sallee FR | title = An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 15 | issue = 11 | pages = 937–974 | date = November 2019 | pmid = 31581854 | doi = 10.1080/17425255.2019.1675636 | s2cid = 203660100 | doi-access = free }}</ref>

=== Mechanism of action === Methylphenidate is a catecholamine reuptake inhibitor that indirectly increases catecholaminergic neurotransmission by inhibiting the dopamine transporter (DAT) and norepinephrine transporter (NET),<ref name="Markowitz_2008">{{cite journal | vauthors = Markowitz JS, Patrick KS | title = Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter? | journal = Journal of Clinical Psychopharmacology | volume = 28 | issue = 3 Suppl 2 | pages = S54–S61 | date = June 2008 | pmid = 18480678 | doi = 10.1097/JCP.0b013e3181733560 }}</ref> which are responsible for clearing catecholamines from the synapse, particularly in the striatum and meso-limbic system.<ref>{{cite journal | vauthors = Schweri MM, Skolnick P, Rafferty MF, Rice KC, Janowsky AJ, Paul SM | title = [3H]Threo-(+/-)-methylphenidate binding to 3,4-dihydroxyphenylethylamine uptake sites in corpus striatum: correlation with the stimulant properties of ritalinic acid esters | journal = Journal of Neurochemistry | volume = 45 | issue = 4 | pages = 1062–1070 | date = October 1985 | pmid = 4031878 | doi = 10.1111/j.1471-4159.1985.tb05524.x | s2cid = 28720285 }}</ref> Moreover, it is thought to "increase the release of these monoamines into the extraneuronal space."<ref name="Focalin XR FDA label">{{cite web | title = Focalin XR- dexmethylphenidate hydrochloride capsule, extended release | date = 27 June 2020 | url = https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a1da905-42a0-4748-9c39-67eca45deccc | access-date = 15 November 2020 | website = DailyMed }}</ref>

In Vitro studies show Methylphenidate possesses weak affinity for 5-HT1A receptors and acts as a partial agonist.<ref>{{cite journal | vauthors = Dipasquale O, Martins D, Sethi A, Veronese M, Hesse S, Rullmann M, Sabri O, Turkheimer F, Harrison NA, Mehta MA, Cercignani M | title = Unravelling the effects of methylphenidate on the dopaminergic and noradrenergic functional circuits | journal = Neuropsychopharmacology | volume = 45 | issue = 9 | pages = 1482–1489 | date = August 2020 | pmid = 32473593 | pmc = 7360745 | doi = 10.1038/s41386-020-0724-x }}</ref>

Methylphenidate, by acting as a negative allosteric modulator of the DAT transporter, prevents dopamine molecules from being absorbed into DAT. This modulation makes DAT less efficient at coupling sodium and chloride gradients to drive inward dopamine transport. Instead, DAT is shifted to the outward-facing state, making it harder to use the sodium gradient (positive charge that normally pulls dopamine inward) and the chloride gradient (negative charge that normally stabilizes the cycle). In this outward conformation, dopamine is “pulled” from the cytosol into the synapse while reuptake is blocked. By keeping DAT outward-facing, sodium coupling is disrupted, chloride coupling is decreased, and inward turnover destabilized. This biases DAT toward outward release, allowing dopamine to leak out without fully coupling to ions. As a result, dopamine is no longer tightly gated by sodium binding, and the firing rate of dopamine from DAT increases.

Methylphenidate increases extracellular dopamine not only by competitively inhibiting reuptake at the dopamine transporter (DAT), but also by modulating DAT conformation through non-substrate-mediated mechanisms. Specifically, methylphenidate acts as a negative allosteric modulator (NAM) at the presynaptic Dopamine Transporter, stabilizing the transporter in its outward-facing conformation. This shift alters the electrochemical gradient and transporter kinetics in a way that promotes dopamine efflux from the presynaptic cytosol into the synaptic cleft even though methylphenidate is not a DAT substrate. This presynaptic Dopamine Transporter Negative allosteric modulation driven efflux amplifies phasic dopamine release and uniquely increases phasic firing rate. This of course in contrast to amphetamines, which reverse DAT via substrate competition and concurrently reduce the dopamine transporter firing rate. Notably, methylphenidate has been shown in studies to induce up to a 500% increase in dopamine release, comparable in magnitude to methamphetamine, though via a non-vesicular, transporter-mediated mechanism. Its 2–3-fold higher DAT binding affinity compared to cocaine may contribute to its more potent and sustained dopaminergic effect.<ref>{{Cite journal | vauthors = Borycz J, Zapata A, Quiroz C, Volkow ND, Ferré S | title = 5-HT1B Receptor-Mediated Serotoninergic Modulation of Methylphenidate-Induced Locomotor Activation in Rats | journal = Neuropsychopharmacology | volume = 33 | issue = 3 | pages = 619–626 | date = February 2008 | doi = 10.1038/sj.npp.1301445 | pmid = 17487226 | url = https://www.nature.com/articles/1301445 | language = en | issn = 1740-634X }}</ref>

This is identical in process to how cocaine leads to an increase in dopamine firing rate and dopamine release into the synapse. However because methylphenidate binds to the DAT transporter with 2-3 fold higher affinity than cocaine this leads to methylphenidate being more powerful as a DAT negative allosteric modulator. Producing a robust dopamine release of 500% equivalent to methamphetamine.<ref>{{Cite journal | vauthors = Hendrickson WA, Ward KB | title = Atomic models for the polypeptide backbones of myohemerythrin and hemerythrin | journal = Biochemical and Biophysical Research Communications | volume = 66 | issue = 4 | pages = 1349–1356 | date = 1975-10-27 | pmid = 5 | doi = 10.1016/0006-291x(75)90508-2 | bibcode = 1975BBRC...66.1349H | issn = 1090-2104 }}</ref>

Although four stereoisomers of methylphenidate (MPH) are possible, only the threo diastereoisomers are used in modern practice. There is a high eudysmic ratio between the SS and RR enantiomers of MPH. Dexmethylphenidate (d-threo-methylphenidate) is a preparation of the RR enantiomer of methylphenidate.<ref>{{cite journal | vauthors = Ding YS, Fowler JS, Volkow ND, Dewey SL, Wang GJ, Logan J, Gatley SJ, Pappas N | title = Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and L-threo-methylphenidate in the human and baboon brain | journal = Psychopharmacology | volume = 131 | issue = 1 | pages = 71–78 | date = May 1997 | pmid = 9181638 | doi = 10.1007/s002130050267 | url = https://zenodo.org/record/1232627 | s2cid = 26046917 }}</ref><ref>{{cite journal | vauthors = Ding YS, Gatley SJ, Thanos PK, Shea C, Garza V, Xu Y, Carter P, King P, Warner D, Taintor NB, Park DJ, Pyatt B, Fowler JS, Volkow ND | title = Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration | journal = Synapse | volume = 53 | issue = 3 | pages = 168–175 | date = September 2004 | pmid = 15236349 | doi = 10.1002/syn.20046 | citeseerx = 10.1.1.514.7833 | s2cid = 11664668 }}</ref> In theory, ''D''-TMP (d-threo-methylphenidate) can be anticipated to be twice the strength of the racemic product.<ref name="Markowitz_2008" /><ref>{{cite journal | vauthors = Davids E, Zhang K, Tarazi FI, Baldessarini RJ | title = Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning | journal = Psychopharmacology | volume = 160 | issue = 1 | pages = 92–98 | date = February 2002 | pmid = 11862378 | doi = 10.1007/s00213-001-0962-5 | s2cid = 8037050 }}</ref>

{| class="wikitable" |- ! Compd<ref name="Williard_2007">{{cite journal | vauthors = Williard RL, Middaugh LD, Zhu HJ, Patrick KS | title = Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity | journal = Behavioural Pharmacology | volume = 18 | issue = 1 | pages = 39–51 | date = February 2007 | pmid = 17218796 | doi = 10.1097/FBP.0b013e3280143226 | s2cid = 20232871 }}</ref> ! DAT (Ki) ! DA (IC50) ! NET (Ki) ! (IC50) |- |D-TMP||161||23||206||39 |- |L-TMP||2250||1600||>10K||980 |- |DL-TMP||121||20||788||51 |- |}

== Chemistry == Dexmethylphenidate a d-threo isomer of methylphenidate which means both chiral centers are in the R configuration. It possesses a Piperidine ring, Phenyl ring and a Methyl Ester group. It is structurally similar to Dopamine and Norepinephrine due to fact that all three molecules contain a Phenethylamine Moiety.<ref>{{Cite web |title=Dexmethylphenidate |url=https://pubchem.ncbi.nlm.nih.gov/compound/154101 |access-date=2025-11-30|language=en| work = PubChem | publisher = U.S. National Library of Medicine }}</ref> It is this similarity that allows Dexmethylphenidate to bind to the Dopamine Transporter (DAT) and the Norepinephrine Transporter (NET).<ref>{{cite journal | vauthors = Liu F, Minami H, Silva RR | title = Dexmethylphenidate hydrochloride in the treatment of attention deficit hyperactivity disorder | journal = Neuropsychiatric Disease and Treatment | volume = 2 | issue = 4 | pages = 467–473 | date = December 2006 | pmid = 19412495 | pmc = 2671958 | doi = 10.2147/nedt.2006.2.4.467 | doi-access = free }}</ref>

== Notes == {{notelist}}

== References == {{Reflist|refs=

<ref name="Daytrana FDA label">{{cite web | title = Daytrana- methylphenidate patch | date = 15 June 2021 | website = DailyMed | url = https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2c312c31-3198-4775-91ab-294e0b4b9e7f | access-date = 26 March 2022 }}</ref>

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{{ADHD pharmacotherapies|state=expanded}} {{Drug use}} {{Stimulants}} {{Monoamine reuptake inhibitors}} {{Sigma receptor modulators}} {{Phenethylamines}} {{Portal bar | Medicine}}

Category:Enantiopure drugs Category:Stimulants Category:2-Benzylpiperidines Category:Drugs developed by Novartis Category:Norepinephrine–dopamine reuptake inhibitors Category:Nootropics Category:Methyl esters Category:Methylphenidate Category:2-Piperidinyl compounds Category:Attention deficit hyperactivity disorder management Category:Wikipedia medicine articles ready to translate