Dexmethylphenidate

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Dexmethylphenidate
Clinical data
Trade namesFocalin, Focalin XR, others
Other namesd-threo-methylphenidate (D-TMP)
AHFS/Drugs.comMonograph
MedlinePlusa603014
License data
Dependence
liability		Physical: None[medical citation needed]; Psychological: High
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability11–52%
Protein binding30%
MetabolismLiver
Elimination half-life4 hours
ExcretionKidney
Identifiers
  • (R,R)-(+)-Methyl 2-phenyl-2-(2-piperidyl)acetate
JSmol)
  • O=C([C@@H]([C@@H]1NCCCC1)C2=CC=CC=C2)OC

  • hydrochloride: Cl.[H][C@@](C(=O)OC)(C1=CC=CC=C1)[C@@]1([H])CCCCN1
  • InChI=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 checkY
  • Key:DUGOZIWVEXMGBE-CHWSQXEVSA-N checkY

  • hydrochloride: InChI=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
  • Key:JUMYIBMBTDDLNG-OJERSXHUSA-N
 ☒NcheckY (what is this?)  (verify)

Dexmethylphenidate, sold under the brand name Focalin among others, is a potent

extended release formulation lasts up to twelve hours.[4] It is the more active enantiomer of methylphenidate.[3]

Common side effects include abdominal pain, loss of appetite, and fever.

seizures, and dangerously prolonged erection.[3] Safety during pregnancy and breastfeeding is unclear.[5] Dexmethylphenidate is a central nervous system (CNS) stimulant.[6][3] How it works in ADHD is unclear.[3]

Dexmethylphenidate was approved for medical use in the United States in 2001.

generic medication.[3] In 2021, it was the 121st most commonly prescribed medication in the United States, with more than 4 million prescriptions.[7][8]

Medical uses

Dexmethylphenidate is used as a treatment for

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.[6]

Improvements in ADHD symptoms in children were significantly greater for dexmethylphenidate XR versus placebo.

OROS) methylphenidate over the first half of the laboratory classroom day but assessments late in the day favoured OROS methylphenidate.[6]

Contraindications

This section is transcluded from Methylphenidate. (edit | history)

Methylphenidate is

heart defects or a hypersensitivity to any ingredients contained in methylphenidate pharmaceuticals.[9]

Pregnant women are advised to only use the medication if the benefits outweigh the potential risks.

teratogenic in rats and rabbits, and that it "is not a major human teratogen".[12]

Adverse effects

Part of this section is transcluded from Methylphenidate. (edit | history)

Products containing dexmethylphenidate have a side effect profile comparable to those containing methylphenidate.[13]

Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. Methylphenidate was ranked 13th in dependence, 12th in physical harm, and 18th in social harm.[14]

The most common side effects associated with methylphenidate (in standard and extended-release formulations) are

Ophthalmologic adverse effects may include blurred vision caused by pupil dilatation and dry eyes, with less frequent reports of diplopia and mydriasis.[contradictory][17][18]

Smokers with ADHD who take methylphenidate may increase their nicotine dependence, and smoke more often than before they began using methylphenidate, with increased nicotine cravings and an average increase of 1.3 cigarettes per day.[19]

There is some evidence of mild reductions in height with prolonged treatment in children.[20] This has been estimated at 1 centimetre (0.4 in) or less per year during the first three years with a total decrease of 3 centimetres (1.2 in) over 10 years.[21][22]

Daytrana patch has a much higher rate of skin reactions than oral methylphenidate.[23]

Methylphenidate can worsen psychosis in people who are psychotic, and in very rare cases it has been associated with the emergence of new psychotic symptoms.[24] It should be used with extreme caution in people with bipolar disorder due to the potential induction of mania or hypomania.[25] There have been very rare reports of suicidal ideation, but some authors claim that evidence does not support a link.[20] Logorrhea is occasionally reported and visual hallucinations are very rarely reported.[17] Priapism is a very rare adverse event that can be potentially serious.[26]

U.S. Food and Drug Administration-commissioned studies in 2011 indicate that in children, young adults, and adults, there is no association between serious adverse

sudden death, heart attack, and stroke) and the medical use of methylphenidate or other ADHD stimulants.[27]

Because some adverse effects may only emerge during chronic use of methylphenidate, a constant watch for adverse effects is recommended.[28]

A 2018

Cochrane review found that methylphenidate might be associated with serious side effects such as heart problems, psychosis, and death. The certainty of the evidence was stated as very low.[29]

The same review found tentative evidence that it may cause both serious and non-serious adverse effects in children.[29][a]

Overdose

The symptoms of a moderate acute overdose on methylphenidate primarily arise from

circulatory collapse.[9][30][31][b]
A methylphenidate overdose is rarely fatal with appropriate care.[31] Following injection of methylphenidate tablets into an artery, severe toxic reactions involving abscess formation and necrosis have been reported.[32]

Treatment of a methylphenidate overdose typically involves the administration of

α-adrenoceptor agonists and propofol serving as second-line therapies.[31]

Packaging of a formulation of methylphenidate advises against crushing the tablets. It is placed under Schedule X of the Indian drug scheduling system. Schedule X medications typically hold abusable medications such as barbiturates or stimulants such as amphetamines.

Addiction and dependence

Methylphenidate is a stimulant with an addiction liability and dependence liability similar to

addictive drugs;[33][34] accordingly, addiction and psychological dependence are possible and likely when methylphenidate is used at high doses as a recreational drug.[34] When used above the medical dose range, stimulants are associated with the development of stimulant psychosis.[35]

Biomolecular mechanisms

Further information: Addiction § Biomolecular mechanisms

Methylphenidate has the potential to induce

pharmacodynamic effect (i.e., dopamine reuptake inhibition) in the brain's reward system. At therapeutic doses, ADHD stimulants do not sufficiently activate the reward system; consequently, when taken as directed in doses that are commonly prescribed for the treatment of ADHD, methylphenidate use lacks the capacity to cause an addiction.[34]

Interactions

This section is transcluded from Methylphenidate. (edit | history)

Methylphenidate may inhibit the metabolism of vitamin K anticoagulants, certain anticonvulsants, and some antidepressants (tricyclic antidepressants, and selective serotonin reuptake inhibitors). Concomitant administration may require dose adjustments, possibly assisted by monitoring of plasma drug concentrations.[36] There are several case reports of methylphenidate inducing serotonin syndrome with concomitant administration of antidepressants.[37][38][39][40]

When methylphenidate is coingested with

hepatic transesterification,[41][42] not unlike the hepatic formation of cocaethylene from cocaine and ethanol. The reduced potency of ethylphenidate and its minor formation means it does not contribute to the pharmacological profile at therapeutic doses and even in overdose cases ethylphenidate concentrations remain negligible.[43][42]

Coingestion of alcohol (ethanol) also increases the blood plasma levels of d-methylphenidate by up to 40%.[44]

Liver toxicity from methylphenidate is extremely rare, but limited evidence suggests that intake of β-adrenergic agonists with methylphenidate may increase the risk of liver toxicity.[45]

Mode of activity

Methylphenidate is a

release of these monoamines into the extraneuronal space."[2]

Although four

racemic product.[46][50]

Compd[51] DAT (Ki) DA (IC50) NET (Ki) NE (IC50)
D-TMP 161 23 206 39
L-TMP 2250 1600 >10K 980
DL-TMP 121 20 788 51

Pharmacology

Main article: 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 DL (dextro-, levo-)-TMP (threo-methylphenidate) XR (extended release) (Concerta, Ritalin LA), with flexible dosing and good tolerability.[52][53] It has also been demonstrated to reduce ADHD symptoms in both children[54] and adults.[55] d-MPH has a similar side-effect profile to MPH[13] and can be administered without regard to food intake.[56]

Notes

  1. ^ "Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non-serious adverse events in children" "Concerning adverse events associated with the treatment, our systematic review of randomised clinical trials (RCTs) demonstrated no increase in serious adverse events, but a high proportion of participants suffered a range of non-serious adverse events."[29]
  2. ^ The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. ... However, fatalities are rare with appropriate care.[31]

References

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  2. ^ a b "Focalin XR- dexmethylphenidate hydrochloride capsule, extended release". DailyMed. 27 June 2020. Retrieved 15 November 2020.
  3. ^ a b c d e f g h "Dexmethylphenidate Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 15 April 2019.
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  9. ^ a b c "Daytrana- methylphenidate patch". DailyMed. 15 June 2021. Retrieved 26 March 2022.
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  27. ^ "FDA drug safety communication: Safety review update of medications used to treat attention-ceficit / hyperactivity disorder (ADHD) in children and young adults". U.S. Food and Drug Administration (FDA). 20 December 2011. Archived from the original on 30 October 2013. Retrieved 4 November 2013. Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, Murray KT, Quinn VP, Stein CM, Callahan ST, Fireman BH, Fish FA, Kirshner HS, O'Duffy A, Connell FA, Ray WA (November 2011). "ADHD drugs and serious cardiovascular events in children and young adults". The New England Journal of Medicine. 365 (20): 1896–1904.
    PMID 22043968
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