Dexmethylphenidate

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Dexmethylphenidate
File:Dexmethylphenidate structure.svg
File:Dextromethylphenidate-based-on-hydrochloride-xtal-1995-3D-balls.png
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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC14H19NO2
Molar mass233.311 g·mol−1
3D model (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 central nervous system (CNS) stimulant used to treat attention deficit hyperactivity disorder (ADHD) in those over the age of five years.[3] It is taken by mouth.[3] The immediate release formulation lasts up to five hours while the 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.[3] Serious side effects may include psychosis, sudden cardiac death, mania, anaphylaxis, 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.[1] It is available as a generic medication.[3] In 2022, it was the 109th most commonly prescribed medication in the United States, with more than 5 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.[6] 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.[6]

Contraindications

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

{{#section-h:Methylphenidate|Contraindications}}

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.[9] {{#section-h:Methylphenidate|Adverse effects}}

Interactions

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

{{#section-h:Methylphenidate|Interactions}}

Mode of activity

Methylphenidate is a catecholamine reuptake inhibitor that indirectly increases catecholaminergic neurotransmission by inhibiting the dopamine transporter (DAT) and norepinephrine transporter (NET),[10] which are responsible for clearing catecholamines from the synapse, particularly in the striatum and meso-limbic system.[11] Moreover, it is thought to "increase the release of these monoamines into the extraneuronal space."[2] 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.[12][13] In theory, D-TMP (d-threo-methylphenidate) can be anticipated to be twice the strength of the racemic product.[10][14]

Compd[15] 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.[16][17] It has also been demonstrated to reduce ADHD symptoms in both children[18] and adults.[19] d-MPH has a similar side-effect profile to MPH[9] and can be administered without regard to food intake.[20] 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.[21][22][23][24][25]

Notes

References

  1. ↑ 1.0 1.1 "Focalin- dexmethylphenidate hydrochloride tablet". DailyMed. 24 June 2020. Retrieved 15 November 2020.
  2. ↑ 2.0 2.1 "Focalin XR- dexmethylphenidate hydrochloride capsule, extended release". DailyMed. 27 June 2020. Retrieved 15 November 2020.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "Dexmethylphenidate Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 15 April 2019.
  4. ↑ Mosby's Drug Reference for Health Professions - E-Book. Elsevier Health Sciences. 2013. p. 455. ISBN 9780323187602.
  5. ↑ "Dexmethylphenidate Use During Pregnancy". Drugs.com. Retrieved 15 April 2019.
  6. ↑ 6.0 6.1 6.2 6.3 Moen MD, Keam SJ (December 2009). "Dexmethylphenidate extended release: a review of its use in the treatment of attention-deficit hyperactivity disorder". CNS Drugs. 23 (12): 1057–83. doi:10.2165/11201140-000000000-00000. PMID 19958043. S2CID 24975170.
  7. ↑ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  8. ↑ "Dexmethylphenidate Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  9. ↑ 9.0 9.1 Keating GM, Figgitt DP (2002). "Dexmethylphenidate". Drugs. 62 (13): 1899–904, discussion 1905–8. doi:10.2165/00003495-200262130-00009. PMID 12215063. S2CID 249894173.
  10. ↑ 10.0 10.1 Markowitz JS, Patrick KS (June 2008). "Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter?". Journal of Clinical Psychopharmacology. 28 (3 Suppl 2): S54-61. doi:10.1097/JCP.0b013e3181733560. PMID 18480678.
  11. ↑ Schweri MM, Skolnick P, Rafferty MF, Rice KC, Janowsky AJ, Paul SM (October 1985). "[3H]Threo-(+/-)-methylphenidate binding to 3,4-dihydroxyphenylethylamine uptake sites in corpus striatum: correlation with the stimulant properties of ritalinic acid esters". Journal of Neurochemistry. 45 (4): 1062–70. doi:10.1111/j.1471-4159.1985.tb05524.x. PMID 4031878. S2CID 28720285.
  12. ↑ Ding YS, Fowler JS, Volkow ND, Dewey SL, Wang GJ, Logan J, et al. (May 1997). "Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and L-threo-methylphenidate in the human and baboon brain". Psychopharmacology. 131 (1): 71–8. doi:10.1007/s002130050267. PMID 9181638. S2CID 26046917.
  13. ↑ Ding YS, Gatley SJ, Thanos PK, Shea C, Garza V, Xu Y, et al. (September 2004). "Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration". Synapse. 53 (3): 168–75. CiteSeerX 10.1.1.514.7833. doi:10.1002/syn.20046. PMID 15236349. S2CID 11664668.
  14. ↑ Davids E, Zhang K, Tarazi FI, Baldessarini RJ (February 2002). "Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning". Psychopharmacology. 160 (1): 92–8. doi:10.1007/s00213-001-0962-5. PMID 11862378. S2CID 8037050.
  15. ↑ Williard RL, Middaugh LD, Zhu HJ, Patrick KS (February 2007). "Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity". Behavioural Pharmacology. 18 (1): 39–51. doi:10.1097/FBP.0b013e3280143226. PMID 17218796. S2CID 20232871.
  16. ↑ McGough JJ, Pataki CS, Suddath R (July 2005). "Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder". Expert Review of Neurotherapeutics. 5 (4): 437–41. doi:10.1586/14737175.5.4.437. PMID 16026226. S2CID 6561452.
  17. ↑ Silva R, Tilker HA, Cecil JT, Kowalik S, Khetani V, Faleck H, et al. (2004). "Open-label study of dexmethylphenidate hydrochloride in children and adolescents with attention deficit hyperactivity disorder". Journal of Child and Adolescent Psychopharmacology. 14 (4): 555–63. doi:10.1089/cap.2004.14.555. PMID 15662147.
  18. ↑ Arnold LE, Lindsay RL, Conners CK, Wigal SB, Levine AJ, Johnson DE, et al. (Winter 2004). "A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder". Journal of Child and Adolescent Psychopharmacology. 14 (4): 542–54. doi:10.1089/cap.2004.14.542. PMID 15662146.
  19. ↑ Spencer TJ, Adler LA, McGough JJ, Muniz R, Jiang H, Pestreich L (June 2007). "Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder". Biological Psychiatry. 61 (12): 1380–7. doi:10.1016/j.biopsych.2006.07.032. PMID 17137560. S2CID 45976373.
  20. ↑ Teo SK, Scheffler MR, Wu A, Stirling DI, Thomas SD, Stypinski D, et al. (February 2004). "A single-dose, two-way crossover, bioequivalence study of dexmethylphenidate HCl with and without food in healthy subjects". Journal of Clinical Pharmacology. 44 (2): 173–8. doi:10.1177/0091270003261899. PMID 14747426. S2CID 20694072.
  21. ↑ Brady LS, Lisanby SH, Gordon JA (3 August 2023). "New directions in psychiatric drug development: promising therapeutics in the pipeline". Expert Opinion on Drug Discovery. 18 (8): 835–850. doi:10.1080/17460441.2023.2224555. PMID 37352473. S2CID 259240509.
  22. ↑ Childress AC, Beltran N, Supnet C, Weiss MD (March 2021). "Reviewing the role of emerging therapies in the ADHD armamentarium". Expert Opinion on Emerging Drugs. 26 (1): 1–16. doi:10.1080/14728214.2020.1846718. PMID 33143485. S2CID 226251694.
  23. ↑ Ryst E, Childress A (2023). "An updated safety review of the current drugs for managing ADHD in children". Expert Opinion on Drug Safety. 22 (11): 1025–1040. doi:10.1080/14740338.2023.2271392. PMID 37843488. S2CID 264144450.
  24. ↑ Harris E (1 February 2018). "Industry update: what is new in the field of therapeutic delivery?". Therapeutic Delivery. 9 (3): 155–161. doi:10.4155/tde-2017-0117.
  25. ↑ Childress AC, Komolova M, Sallee FR (November 2019). "An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations". Expert Opinion on Drug Metabolism & Toxicology. 15 (11): 937–974. doi:10.1080/17425255.2019.1675636. PMID 31581854. S2CID 203660100.
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