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Identification
Name Methylphenidate
Accession Number DB00422 (APRD00657)
Type small molecule
Groups approved
Description

A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • d-methylphenidate HCl
  • Methyl phenidyl acetate
  • methylphenidate
  • Methylphenidate HCl
  • Methylphenidate hydrochloride
  • Methylphenidatum [INN-Latin]
  • Methylphenidylacetate hydrochloride
  • Metilfenidat hydrochloride
  • Metilfenidato [INN-Spanish]
  • Metilfenidato [Italian]
  • Phenidylate
Brand names
  • 4311/B Ciba
  • Calocain
  • Centedein
  • Centedrin
  • Centedrine
  • Centredin
  • Concerta
  • Daytrana
  • Focalin
  • Focalin XR
  • Meridil
  • Metadate
  • Metadate CD
  • Metadate ER
  • Methylin
  • Methylin ER
  • Methylofenidan
  • Methylphen
  • Methylphenidan
  • Methypatch
  • Plimasine
  • PMS-Methylphenidate
  • Riphenidate
  • Ritalin
  • Ritalin hydrochloride
  • Ritalin LA
  • Ritalin SR
  • Ritalin-SR
  • Ritaline
  • Ritcher Works
Brand name mixtures Not Available
Categories
  • Adrenergic Agents
  • Dopamine Uptake Inhibitors
  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Sympathomimetics
CAS number 113-45-1
Weight Average: 233.3062
Monoisotopic: 233.141578857
Chemical Formula C14H19NO2
InChI Key InChIKey=DUGOZIWVEXMGBE-UHFFFAOYSA-N
InChI
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
Plain Text
IUPAC Name
methyl 2-phenyl-2-(piperidin-2-yl)acetate
SMILES
COC(=O)C(C1CCCCN1)C1=CC=CC=C1
Plain Text
Mass Spec show (7.8 KB)
Taxonomy
Kingdom Organic
Classes
  • Phenylacetates
  • Phenethylamines
  • Amphetamines
Substructures
  • Carboxylic Acids and Derivatives
  • Acetates
  • Aliphatic and Aryl Amines
  • Phenylacetates
  • Ethers
  • Benzene and Derivatives
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Amphetamines
  • Piperidines
Pharmacology
Indication For use as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity.
Pharmacodynamics Methylphenidate is a central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine.
Mechanism of action Methylphenidate blocks dopamine uptake in central adrenergic neurons by blocking dopamine transport or carrier proteins. Methylphenidate acts at the brain stem arousal system and the cerebral cortex and causes increased sympathomimetic activity in the central nervous system. Alteration of serotonergic pathways via changes in dopamine transport may result.
Absorption Readily absorbed in a biphasic manner. It reaches peak absorption at approximately two hours for the first phase and five hours for the second phase. Bioavailability is low (approximately 30%)
Volume of distribution Not Available
Protein binding Low (approximately 15%)
Metabolism

Hepatic, methylphenidate is metabolized primarily by de-esterification to ritalinic acid (α-phenyl-2-piperidine acetic acid, PPAA), which has little to no pharmacologic activity.
Route of elimination Not Available
Half life 2.4 hours in children and 2.1 hours in adults
Clearance Not Available
Toxicity Symptoms of overdose include vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, and dryness of mucous membranes. LD50=190mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Shire development inc
  • Ucb inc
  • Novartis pharmaceuticals corp
  • Mallinckrodt inc
  • Tris pharma inc
  • Ortho mcneil janssen pharmaceutical inc
  • Able laboratories inc
  • Actavis elizabeth llc
  • Watson laboratories inc
  • Ortho-McNeil-Janssen Pharmaceuticals, Inc.
Packagers
Dosage forms
Form Route Strength
Capsule, extended release Oral
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Daytrana 30 15 mg/9hr Patches Box 175.64 USD box
Daytrana 30 30 mg/9hr Patches Box 174.73 USD box
Daytrana 30 10 mg/9hr Patches Box 172.78 USD box
Daytrana 30 20 mg/9hr Patches Box 168.72 USD box
Methylphenidate hcl powder 44.62 USD g
Concerta er 54 mg tablet 25.45 USD tablet
Concerta er 36 mg tablet 23.38 USD tablet
Concerta er 27 mg tablet 22.65 USD tablet
Concerta er 18 mg tablet 22.11 USD tablet
Metadate cd 50 mg capsule 7.08 USD capsule
Metadate cd 60 mg capsule 7.02 USD capsule
Concerta 54 mg Controlled Release Tabs 6.18 USD tab
Metadate cd 40 mg capsule 5.77 USD capsule
Concerta 36 mg Controlled Release Tabs 5.72 USD tab
Focalin xr 30 mg capsule 5.42 USD capsule
Focalin XR 20 mg 24 Hour Capsule 5.31 USD capsule
Daytrana 10 mg/9 hr patch 5.16 USD patch
Daytrana 15 mg/9 hr patch 5.16 USD patch
Daytrana 20 mg/9 hour patch 5.16 USD patch
Daytrana 30 mg/9 hour patch 5.16 USD patch
Focalin xr 15 mg capsule 5.16 USD capsule
Focalin xr 20 mg capsule 5.16 USD capsule
Focalin XR 30 mg 24 Hour Capsule 5.15 USD capsule
Focalin xr 10 mg capsule 5.02 USD capsule
Concerta 18 mg Controlled Release Tabs 5.0 USD tab
Concerta 27 mg Controlled Release Tabs 5.0 USD tab
Focalin XR 10 mg 24 Hour Capsule 4.96 USD capsule
Focalin xr 5 mg capsule 4.95 USD capsule
Concerta 54 mg tablet sa 4.91 USD tablet
Focalin XR 15 mg 24 Hour Capsule 4.89 USD capsule
Focalin XR 5 mg 24 Hour Capsule 4.83 USD capsule
Ritalin la 40 mg capsule 4.55 USD capsule
Concerta 36 mg tablet sa 4.51 USD tablet
Ritalin la 30 mg capsule 4.43 USD capsule
Ritalin LA 10 mg 24 Hour Capsule 4.42 USD capsule
Ritalin LA 20 mg 24 Hour Capsule 4.42 USD capsule
Ritalin LA 30 mg 24 Hour Capsule 4.42 USD capsule
Ritalin LA 40 mg 24 Hour Capsule 4.42 USD capsule
Concerta 27 mg tablet sa 4.37 USD tablet
Ritalin la 10 mg capsule 4.33 USD capsule
Ritalin la 20 mg capsule 4.33 USD capsule
Concerta 18 mg tablet sa 4.27 USD tablet
Metadate cd 20 mg capsule 4.24 USD capsule
Metadate cd 30 mg capsule 4.24 USD capsule
Metadate cd 10 mg capsule 4.2 USD capsule
Methylphenidate er 10 mg tablet 3.24 USD tablet
Ritalin SR 20 mg Controlled Release Tabs 3.0 USD tab
Ritalin sr 20 mg tablet 2.67 USD tablet
Ritalin 20 mg tablet 1.87 USD tablet
Focalin 10 mg tablet 1.7 USD tablet
Ritalin 5 mg tablet 1.42 USD tablet
Metadate er 20 mg tablet 1.32 USD tablet
Methylin ER 20 mg Controlled Release Tabs 1.3 USD tab
Ritalin 10 mg tablet 1.29 USD tablet
Metadate er 10 mg tablet sa 1.28 USD tablet
Focalin 5 mg tablet 1.26 USD tablet
Methylphenidate HCl CR 20 mg Controlled Release Tabs 1.2 USD tab
Methylin er 20 mg tablet 1.12 USD tablet
Methylphenidate HCl 20 mg tablet 1.05 USD tablet
Methylin ER 10 mg 1.0 USD tab
Methylphenidate HCl 10 mg tablet 0.95 USD tablet
Methylphenidate HCl 5 mg tablet 0.94 USD tablet
Methylin er 10 mg tablet 0.84 USD tablet
Focalin 2.5 mg tablet 0.76 USD tablet
Methylin 20 mg tablet 0.69 USD tablet
Methylphenidate 20 mg tablet 0.69 USD tablet
Ritalin 20 mg Tablet 0.67 USD tablet
Ritalin Sr 20 mg Extended-Release Tablet 0.67 USD tablet
Methylin 10 mg tablet 0.48 USD tablet
Methylphenidate 10 mg tablet 0.48 USD tablet
Ritalin 10 mg Tablet 0.38 USD tablet
Apo-Methylphenidate 20 mg Tablet 0.37 USD tablet
Apo-Methylphenidate Sr 20 mg Extended-Release Tablet 0.37 USD tablet
Pms-Methylphenidate 20 mg Tablet 0.37 USD tablet
Sandoz Methylphenidate 20 mg Extended-Release Tablet 0.37 USD tablet
Methylin 5 mg tablet 0.33 USD tablet
Methylphenidate 5 mg tablet 0.33 USD tablet
Apo-Methylphenidate 10 mg Tablet 0.17 USD tablet
Pms-Methylphenidate 10 mg Tablet 0.17 USD tablet
Pms-Methylphenidate 5 mg Tablet 0.1 USD tablet
Patents
Country Patent Number Approved Expires
United States 7691880 2004-10-07 2024-10-07
United States 5958446 1992-12-12 2012-12-12
Canada 2355644 2009-01-20 2019-12-17
Canada 2264852 2005-11-01 2017-09-16
Properties
State solid
Melting point 224-226oC
Experimental Properties
Property Value Source
water solubility 1255mg/L PhysProp
logP 2.1 PhysProp
pKa 8.77 Various sources
Predicted Properties
Property Value Source
water solubility 1.82e-01 g/l ALOGPS
logP 1.47 ALOGPS
logP 2.25 ChemAxon Molconvert
logS -3.11 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 38.33 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 66.73 ChemAxon Molconvert
polarizability 26.21 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Keating GM, McClellan K, Jarvis B: Methylphenidate (OROS formulation). CNS Drugs. 2001;15(6):495-500; discussion 501-3. Pubmed
  2. Markowitz JS, DeVane CL, Pestreich LK, Patrick KS, Muniz R: A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an exploratory study. J Child Adolesc Psychopharmacol. 2006 Dec;16(6):687-98. Pubmed
  3. Fone KC, Nutt DJ: Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder. Curr Opin Pharmacol. 2005 Feb;5(1):87-93. Pubmed
  4. Sharma RP, Javaid JI, Pandey GN, Easton M, Davis JM: Pharmacological effects of methylphenidate on plasma homovanillic acid and growth hormone. Psychiatry Res. 1990 Apr;32(1):9-17. Pubmed
  5. Shults T, Kownacki AA, Woods WE, Valentine R, Dougherty J, Tobin T: Pharmacokinetics and behavioral effects of methylphenidate in Thoroughbred horses. Am J Vet Res. 1981 May;42(5):722-6. Pubmed
External Links
Resource Link
KEGG Drug D04999 Link_out
KEGG Compound C07196 Link_out
PubChem Compound 4158 Link_out
PubChem Substance 46505929 Link_out
ChemSpider 4015 Link_out
ChEBI 6887 Link_out
ChEMBL 6887 Link_out
Therapeutic Targets Database DAP000024 Link_out
PharmGKB PA450464 Link_out
Drug Product Database 2249332 Link_out
RxList http://www.rxlist.com/cgi/generic/methphen.htm Link_out
Drugs.com http://www.drugs.com/methylphenidate.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/rit1383.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Methylphenidate Link_out
ATC Codes
  • N06BA04
AHFS Codes
  • 28:20.92
PDB Entries Not Available
FDA label show (178.3 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Take on empty stomach: 1 hour before or 2 hours after meals.
Targets

1. Sodium-dependent dopamine transporter

Pharmacological action: yes
Actions: inhibitor

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: Q01959 Link_out
Gene: SLC6A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Volkow ND, Fowler JS, Gatley SJ, Dewey SL, Wang GJ, Logan J, Ding YS, Franceschi D, Gifford A, Morgan A, Pappas N, King P: Comparable changes in synaptic dopamine induced by methylphenidate and by cocaine in the baboon brain. Synapse. 1999 Jan;31(1):59-66. Pubmed
  2. Wayment HK, Deutsch H, Schweri MM, Schenk JO: Effects of methylphenidate analogues on phenethylamine substrates for the striatal dopamine transporter: potential as amphetamine antagonists? J Neurochem. 1999 Mar;72(3):1266-74. Pubmed
  3. Dresel SH, Kung MP, Huang X, Plossl K, Hou C, Shiue CY, Karp J, Kung HF: In vivo imaging of serotonin transporters with [99mTc]TRODAT-1 in nonhuman primates. Eur J Nucl Med. 1999 Apr;26(4):342-7. Pubmed
  4. Volkow ND, Wang GJ, Fowler JS, Fischman M, Foltin R, Abumrad NN, Gatley SJ, Logan J, Wong C, Gifford A, Ding YS, Hitzemann R, Pappas N: Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain. Life Sci. 1999;65(1):PL7-12. Pubmed
  5. Izenwasser S, Coy AE, Ladenheim B, Loeloff RJ, Cadet JL, French D: Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine. Eur J Pharmacol. 1999 Jun 4;373(2-3):187-93. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed
  8. Viggiano D, Vallone D, Sadile A: Dysfunctions in dopamine systems and ADHD: evidence from animals and modeling. Neural Plast. 2004;11(1-2):97-114. Pubmed
  9. Tilley MR, Gu HH: The effects of methylphenidate on knockin mice with a methylphenidate-resistant dopamine transporter. J Pharmacol Exp Ther. 2008 Nov;327(2):554-60. Epub 2008 Aug 12. Pubmed

2. Sodium-dependent noradrenaline transporter

Pharmacological action: unknown
Actions: inhibitor

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yang L, Wang YF, Li J, Faraone SV: Association of norepinephrine transporter gene with methylphenidate response. J Am Acad Child Adolesc Psychiatry. 2004 Sep;43(9):1154-8. Pubmed
  2. Williard RL, Middaugh LD, Zhu HJ, Patrick KS: Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity. Behav Pharmacol. 2007 Feb;18(1):39-51. Pubmed
  3. Chuhan YS, Taukulis HK: Impairment of single-trial memory formation by oral methylphenidate in the rat. Neurobiol Learn Mem. 2006 Mar;85(2):125-31. Epub 2005 Oct 24. Pubmed
  4. Gray JD, Punsoni M, Tabori NE, Melton JT, Fanslow V, Ward MJ, Zupan B, Menzer D, Rice J, Drake CT, Romeo RD, Brake WG, Torres-Reveron A, Milner TA: Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress. J Neurosci. 2007 Jul 4;27(27):7196-207. Pubmed
  5. Sandoval V, Riddle EL, Ugarte YV, Hanson GR, Fleckenstein AE: Methamphetamine-induced rapid and reversible changes in dopamine transporter function: an in vitro model. J Neurosci. 2001 Feb 15;21(4):1413-9. Pubmed
  6. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed
  7. Tilley MR, Gu HH: The effects of methylphenidate on knockin mice with a methylphenidate-resistant dopamine transporter. J Pharmacol Exp Ther. 2008 Nov;327(2):554-60. Epub 2008 Aug 12. Pubmed

3. Sodium-dependent serotonin transporter

Pharmacological action: unknown
Actions: inhibitor

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dresel SH, Kung MP, Huang X, Plossl K, Hou C, Shiue CY, Karp J, Kung HF: In vivo imaging of serotonin transporters with [99mTc]TRODAT-1 in nonhuman primates. Eur J Nucl Med. 1999 Apr;26(4):342-7. Pubmed
  2. Izenwasser S, Coy AE, Ladenheim B, Loeloff RJ, Cadet JL, French D: Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine. Eur J Pharmacol. 1999 Jun 4;373(2-3):187-93. Pubmed
  3. Stehouwer JS, Jarkas N, Zeng F, Voll RJ, Williams L, Owens MJ, Votaw JR, Goodman MM: Synthesis, radiosynthesis, and biological evaluation of carbon-11 labeled 2beta-carbomethoxy-3beta-(3’-((Z)-2-haloethenyl)phenyl)nortropanes: candidate radioligands for in vivo imaging of the serotonin transporter with positron emission tomography. J Med Chem. 2006 Nov 16;49(23):6760-7. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:03

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.