Editing Dexmethylphenidate (section)

=== 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
|-
|}