Dexmethylphenidate

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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>Template:Cite book</ref> It is the more active enantiomer of methylphenidate.<ref name="AHFS2019" />

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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Dexmethylphenidate was approved for medical use in the United States in 2001.<ref name="Focalin FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is available as a generic medication.<ref name=AHFS2019/> In 2022, it was the 109th most commonly prescribed medication in the United States, with more than 5Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Template: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=Moen2009>Template:Cite journal</ref>

Improvements in ADHD symptoms in children were significantly greater for dexmethylphenidate XR versus placebo.<ref name=Moen2009/> 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=Moen2009 />

Adverse effects

Template:Transcluded section Products containing dexmethylphenidate have a side effect profile comparable to those containing methylphenidate.<ref name="Dexmethylphenidate">Template:Cite journal</ref> Template:Trim

Pharmacology

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} 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>Template:Cite journal</ref><ref>Template:Cite journal</ref> It has also been demonstrated to reduce ADHD symptoms in both children<ref>Template:Cite journal</ref> and adults.<ref>Template:Cite journal</ref> d-MPH has a similar side-effect profile to MPH<ref name="Dexmethylphenidate" /> and can be administered without regard to food intake.<ref>Template:Cite journal</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>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</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">Template:Cite journal</ref> which are responsible for clearing catecholamines from the synapse, particularly in the striatum and meso-limbic system.<ref>Template:Cite journal</ref> Moreover, it is thought to "increase the release of these monoamines into the extraneuronal space."<ref name="Focalin XR FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</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>Template:Cite journal</ref><ref>Template:Cite journal</ref> In theory, D-TMP (d-threo-methylphenidate) can be anticipated to be twice the strength of the racemic product.<ref name="MarkowitzPatrick2008" /><ref>Template:Cite journal</ref>

Compd<ref name="Williard">Template:Cite journal</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

References

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