Editing Dexmethylphenidate (section)

== Pharmacology==
{{main|Methylphenidate#Pharmacology}}
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 <small>DL (dextro-, levo-)</small>-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 = 437–41 | 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 = 555–63 | 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 = 542–54 | date =Winter 2004 | pmid = 15662146 | doi = 10.1089/cap.2004.14.542}}</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 = 1380–7 | 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 = 173–8 | 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 |date=1 February 2018 |volume=9 |issue=3 |pages=155–161 |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="MarkowitzPatrick2008">{{cite journal |vauthors=Markowitz JS, Patrick KS |date=June 2008 |title=Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter? |journal=Journal of Clinical Psychopharmacology |volume=28 |issue=3 Suppl 2 |pages=S54-61 |doi=10.1097/JCP.0b013e3181733560 |pmid=18480678}}</ref> which are responsible for clearing catecholamines from the [[synapse]], particularly in the [[striatum]] and [[limbic system|meso-limbic system]].<ref>{{cite journal |vauthors=Schweri MM, Skolnick P, Rafferty MF, Rice KC, Janowsky AJ, Paul SM |date=October 1985 |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=1062–70 |doi=10.1111/j.1471-4159.1985.tb05524.x |pmid=4031878 |s2cid=28720285}}</ref> Moreover, it is thought to "increase the [[releasing agent|release]] of these monoamines into the extraneuronal space."<ref name="Focalin XR FDA label">{{cite web |date=27 June 2020 |title=Focalin XR- dexmethylphenidate hydrochloride capsule, extended release |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a1da905-42a0-4748-9c39-67eca45deccc |access-date=15 November 2020 |website=DailyMed}}</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 |date=May 1997 |title=Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and L-threo-methylphenidate in the human and baboon brain |url=https://zenodo.org/record/1232627 |journal=Psychopharmacology |volume=131 |issue=1 |pages=71–8 |doi=10.1007/s002130050267 |pmid=9181638 |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 |date=September 2004 |title=Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration |journal=Synapse |volume=53 |issue=3 |pages=168–75 |citeseerx=10.1.1.514.7833 |doi=10.1002/syn.20046 |pmid=15236349 |s2cid=11664668}}</ref> In theory, ''D''-TMP (d-threo-methylphenidate) can be anticipated to be twice the strength of the [[racemic]] product.<ref name="MarkowitzPatrick2008" /><ref>{{cite journal |vauthors=Davids E, Zhang K, Tarazi FI, Baldessarini RJ |date=February 2002 |title=Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning |journal=Psychopharmacology |volume=160 |issue=1 |pages=92–8 |doi=10.1007/s00213-001-0962-5 |pmid=11862378 |s2cid=8037050}}</ref>

{| class="wikitable"
|-
! Compd<ref name="Williard">{{cite journal |vauthors=Williard RL, Middaugh LD, Zhu HJ, Patrick KS |date=February 2007 |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 |doi=10.1097/FBP.0b013e3280143226 |pmid=17218796 |s2cid=20232871}}</ref>
! DAT (K<sub>i</sub>)
! DA (IC<sub>50</sub>)
! NET (K<sub>i</sub>)
! (IC<sub>50</sub>)
|-
|<small>D</small>-TMP||161||23||206||39
|-
|<small>L</small>-TMP||2250||1600||>10K||980
|-
|<small>DL</small>-TMP||121||20||788||51
|-
|}