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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2018-05-20 20:50:55 UTC
HMDB IDHMDB0014566
Secondary Accession Numbers
  • HMDB14566
Metabolite Identification
Common NameMethylphenidate
DescriptionMethylphenidate is only found in individuals that have used or taken this drug. It 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. [PubChem]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.
Structure
Thumb
Synonyms
ValueSource
alpha-Phenyl-2-piperidineacetic acid methyl esterChEBI
Methyl alpha-phenyl-alpha-(2-piperidyl)acetateChEBI
Methyl alpha-phenyl-alpha-2-piperidinylacetateChEBI
Methyl phenidylacetateChEBI
MethylphenidanChEBI
a-Phenyl-2-piperidineacetate methyl esterGenerator
a-Phenyl-2-piperidineacetic acid methyl esterGenerator
alpha-Phenyl-2-piperidineacetate methyl esterGenerator
α-phenyl-2-piperidineacetate methyl esterGenerator
α-phenyl-2-piperidineacetic acid methyl esterGenerator
Methylphenidic acidGenerator
Methyl a-phenyl-a-(2-piperidyl)acetateGenerator
Methyl a-phenyl-a-(2-piperidyl)acetic acidGenerator
Methyl alpha-phenyl-alpha-(2-piperidyl)acetic acidGenerator
Methyl α-phenyl-α-(2-piperidyl)acetateGenerator
Methyl α-phenyl-α-(2-piperidyl)acetic acidGenerator
Methyl a-phenyl-a-2-piperidinylacetateGenerator
Methyl a-phenyl-a-2-piperidinylacetic acidGenerator
Methyl alpha-phenyl-alpha-2-piperidinylacetic acidGenerator
Methyl α-phenyl-α-2-piperidinylacetateGenerator
Methyl α-phenyl-α-2-piperidinylacetic acidGenerator
Methyl phenidylacetic acidGenerator
D-Methylphenidate HCLHMDB
Methyl phenidyl acetateHMDB
Methylphenidate HCLHMDB
Methylphenidate hydrochlorideHMDB
Methylphenidylacetate hydrochlorideHMDB
Metilfenidat hydrochlorideHMDB
PhenidylateHMDB
MethylinMeSH
Novartis brand 1 OF methylphenidate hydrochlorideMeSH
RitalineMeSH
CentedrinMeSH
ConcertaMeSH
EquasymMeSH
Hydrochloride, methylphenidateMeSH
MetadateMeSH
Cephalon brand OF methylphenidate hydrochlorideMeSH
DaytranaMeSH
RitalinMeSH
Ritalin SRMeSH
TsentedrinMeSH
Celltech brand OF methylphenidate hydrochlorideMeSH
Mallinckrodt brand OF methylphenidate hydrochlorideMeSH
Novartis brand 2 OF methylphenidate hydrochlorideMeSH
Ritalin-SRMeSH
Chemical FormulaC14H19NO2
Average Molecular Weight233.3062
Monoisotopic Molecular Weight233.141578857
IUPAC Namemethyl 2-phenyl-2-(piperidin-2-yl)acetate
Traditional Namemethylphenidate
CAS Registry Number113-45-1
SMILES
COC(=O)C(C1CCCCN1)C1=CC=CC=C1
InChI Identifier
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
InChI KeyDUGOZIWVEXMGBE-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassAmines
Direct ParentAralkylamines
Alternative Parents
Substituents
  • Aralkylamine
  • Monocyclic benzene moiety
  • Piperidine
  • Benzenoid
  • Methyl ester
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Carboxylic acid derivative
  • Secondary aliphatic amine
  • Monocarboxylic acid or derivatives
  • Secondary amine
  • Azacycle
  • Organoheterocyclic compound
  • Organopnictogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxygen compound
  • Organic oxide
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point224 - 226 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.18 g/LNot Available
LogP2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.18 g/LALOGPS
logP1.47ALOGPS
logP2.25ChemAxon
logS-3.1ALOGPS
pKa (Strongest Basic)9.09ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area38.33 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity66.73 m³·mol⁻¹ChemAxon
Polarizability26.21 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-001i-0090000000-b461cd02e59ebf84d3f9View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001i-9100000000-c75de12fbdae54dce658View in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-001i-0090000000-b461cd02e59ebf84d3f9View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001i-9100000000-c75de12fbdae54dce658View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0089-9610000000-8e4c1241e36274356032View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-1190000000-8803b6fb1d54baf20a6fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-6390000000-63f6ddbd32540d6c0e4eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9500000000-dab6b5667313005cbcd2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0090000000-dbf1d73eb0c9410efbf6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-2290000000-4a7ee5089439605a9759View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00w9-9520000000-aa484f1df63a11905d5aView in MoNA
MSMass Spectrum (Electron Ionization)splash10-001i-9100000000-1a9c5badbee827946da1View in MoNA
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00422 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00422 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00422
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4015
KEGG Compound IDC07196
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMethylphenidate
METLIN IDNot Available
PubChem Compound4158
PDB IDNot Available
ChEBI ID84276
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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:15661631 ]
  2. 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:2190251 ]
  3. 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:7258793 ]
  4. Keating GM, McClellan K, Jarvis B: Methylphenidate (OROS formulation). CNS Drugs. 2001;15(6):495-500; discussion 501-3. [PubMed:11524026 ]
  5. 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:17201613 ]
  6. (). FDA label . .

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
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.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in neurotransmitter:sodium symporter activity
Specific function:
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A3
Uniprot ID:
Q01959
Molecular weight:
68494.255
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:10025684 ]
  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:10037500 ]
  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:10199939 ]
  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:10403500 ]
  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:10414438 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  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:9537821 ]
  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:15303308 ]
  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. doi: 10.1124/jpet.108.141713. Epub 2008 Aug 12. [PubMed:18698001 ]

Transporters

General function:
Involved in neurotransmitter:sodium symporter activity
Specific function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular weight:
69331.42
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:15322419 ]
  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:17218796 ]
  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:16246598 ]
  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:17611273 ]
  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:11160413 ]
  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:9537821 ]
  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. doi: 10.1124/jpet.108.141713. Epub 2008 Aug 12. [PubMed:18698001 ]
General function:
Involved in neurotransmitter:sodium symporter activity
Specific function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular weight:
70324.165
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:10199939 ]
  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:10414438 ]
  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:17154506 ]