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Showing drug card for Methylphenidate (DB00422)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:55
Primary Accession Number DB00422
Secondary Accession Number
  • APRD00657
Name Methylphenidate
Drug Type
  • Approved
  • Investigational
  • Small Molecule
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]
Synonyms
  1. Methyl phenidyl acetate
  2. Methylphenidate HCl
  3. Methylphenidate hydrochloride
  4. Methylphenidatum [INN-Latin]
  5. Methylphenidylacetate hydrochloride
  6. Metilfenidat hydrochloride
  7. Metilfenidato [INN-Spanish]
  8. Metilfenidato [Italian]
  9. Phenidylate
  10. d-methylphenidate HCl
  11. methylphenidate
Brand Names
  1. 4311/B Ciba
  2. Calocain
  3. Centedein
  4. Centedrin
  5. Centedrine
  6. Centredin
  7. Concerta
  8. Daytrana
  9. Focalin
  10. Focalin XR
  11. Meridil
  12. Metadate
  13. Metadate CD
  14. Metadate ER
  15. Methylin
  16. Methylin ER
  17. Methylofenidan
  18. Methylphen
  19. Methylphenidan
  20. Methypatch
  21. PMS-Methylphenidate
  22. Plimasine
  23. Riphenidate
  24. Ritalin
  25. Ritalin LA
  26. Ritalin SR
  27. Ritalin hydrochloride
  28. Ritalin-SR
  29. Ritaline
  30. Ritcher Works
Brand Mixtures Not Available
Chemical IUPAC Name methyl 2-phenyl-2-piperidin-2-ylacetate
Chemical Formula C14H19NO2
Chemical Structure Structure
CAS Registry Number 113-45-1
InChI Identifier InChI=1/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 Key DUGOZIWVEXMGBE-UHFFFAOYAU
KEGG Drug D04999 Link Image
KEGG Compound C07196 Link Image
PubChem Compound 4158 Link Image
PubChem Substance 7854358 Link Image
ChEBI ID Not Available
PharmGKB ID PA450464 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02249332 Link Image
RxList Link http://www.rxlist.com/cgi/generic/methphen.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/rit1383.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Methylphenidate Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference M. Hartmann, L. Panizzon, U.S. Pat. 2,507,631 (1950)
Average Molecular Weight 233.3062
Monoisotopic Molecular Weight 233.1416
State Solid
Melting Point 224-226oC
Experimental Water Solubility 1255mg/L Source: PhysProp
Predicted Water Solubility 1.82e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.1 Source: PhysProp
Predicted LogP 1.47 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.11 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 8.77
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES COC(=O)[C@@H]([C@H]1CCCCN1)C1=CC=CC=C1
Canonical SMILES COC(=O)C(C1CCCCN1)C1=CC=CC=C1
Drug Category
  • Adrenergic Agents
  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Dopamine Uptake Inhibitors
  • Sympathomimetics
ATC Codes
AHFS Codes
  • 28:20.92
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.
Pharmacology 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%)
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)
Protein Binding Low (approximately 15%)
Biotransformation 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.
Half Life 2.4 hours in children and 2.1 hours in adults
Dosage Forms
Form Route
Capsule, extended release Oral
Tablet Oral
Tablet, extended release Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Carbamazepine Carbamazepine could reduce the effect of methylphendiate
Cyclosporine Methylphenidate increases the effect and toxicity of cyclosporine
Guanethidine The agent decreases the effect of guanethidine
Isocarboxazid Possible hypertensive crisis with this combination
Phenelzine Possible hypertensive crisis with this combination
Rasagiline Possible hypertensive crisis with this combination
Tranylcypromine Possible hypertensive crisis with this combination
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Take on empty stomach: 1 hour before or 2 hours after meals.
Pathways Not Available
General References
  1. Keating GM, McClellan K, Jarvis B: Methylphenidate (OROS formulation). CNS Drugs. 2001;15(6):495-500; discussion 501-3. [PubMed Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
  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 Link Image]
  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 Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
  8. RxList Link Image
  9. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Sodium-dependent noradrenaline transporter
  2. Sodium-dependent dopamine transporter
  3. Sodium-dependent serotonin transporter
Drug Target 1 [top]
Target 1 ID 540
Target 1 Name Sodium-dependent noradrenaline transporter
Target 1 Synonyms
  1. NET
  2. Norepinephrine transporter
Target 1 Gene Name SLC6A2
Target 1 Protein Sequence >Sodium-dependent noradrenaline transporter 
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWG
KKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYN
REGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTW
NSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLC
LMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFY
RLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFA
IFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSS
MGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTS
ILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINF
KPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHL
VAQRDIRQFQLQHWLAI
Target 1 Number of Residues 627
Target 1 Molecular Weight 69333
Target 1 Theoretical pI 7.53
Target 1 GO Classification
Function
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity
Process
physiological process
cellular physiological process
transport
neurotransmitter transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane
Target 1 General Function Involved in neurotransmitter:sodium symporter activity
Target 1 Specific Function Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 65-85
  • 93-112
  • 136-156
  • 235-253
  • 262-279
  • 315-332
  • 344-365
  • 398-417
  • 444-462
  • 478-498
  • 519-538
  • 557-575
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 189258 Link Image
Target 1 UniProtKB/Swiss-Prot ID P23975 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name SC6A2_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1854 bp 
ATGCTTCTGGCGCGGATGAACCCGCAGGTGCAGCCCGAGAACAACGGGGCGGACACGGGT
CCAGAGCAGCCCCTTCGGGCGCGCAAAACTGCGGAGCTGCTGGTGGTGAAGGAGCGCAAC
GGCGTCCAGTGCCTGCTGGCGCCCCGCGACGGCGACGCGCAGCCCCGGGAGACCTGGGGC
AAGAAGATCGACTTCCTGCTGTCCGTAGTCGGCTTCGCAGTGGACCTGGCCAACGTGTGG
CGCTTCCCCTACCTCTGCTACAAGAACGGCGGCGGTGCCTTCTTGATCCCGTACACACTG
TTCCTTATCATCGCGGGGATGCCCCTGTTCTACATGGAGCTGGCTCTGGGACAGTACAAC
CGGGAGGGGGCTGCCACCGTTTGGAAAATCTGCCCATTCTTCAAAGGCGTTGGCTATGCT
GTCATCCTGATCGCCCTGTACGTTGGCTTCTACTACAACGTCATCATCGCCTGGTCACTC
TACTACCTCTTCTCCTCCTTCACCCTCAACCTGCCCTGGACCGACTGTGGCCACACCTGG
AACAGCCCCAACTGTACCGACCCCAAGCTCCTCAATGGCTCCGTGCTTGGCAACCACACC
AAGTACTCCAAGTACAAGTTCACGCCGGCAGCCGAGTTTTATGAGCGTGGTGTCCTGCAC
CTTCACGAGAGCAGCGGGATTCATGACATCGGCCTGCCCCAGTGGCAGCTCTTGCTCTGT
CTGATGGTCGTCGTCATCGTCTTGTATTTTAGCCTCTGGAAAGGGGTGAAGACATCAGGA
AAGGTGGTGTGGATCACAGCCACGCTGCCTTACTTCGTGCTGTTCGTGCTCCTGGTCCAT
GGCGTCACGCTGCCCGGAGCCTCCAATGGCATCAATGCCTACCTGCACATCGACTTCTAC
CGCTTGAAAGAGGCCACGGTATGGATTGATGCCGCAACTCAGATATTTTTTTCCTTGGGG
GCTGGATTTGGAGTATTGATTGCATTTGCCAGTTACAACAAATTTGACAACAACTGTTAC
AGGGATGCCCTGCTGACCAGCAGCATCAACTGTATCACCAGCTTCGTCTCTGGGTTCGCC
ATCTTCTCCATCCTTGGTTACATGGCCCATGAACACAAGGTCAACATTGAGGATGTGGCC
ACAGAAGGAGCTGGCCTAGTGTTCATCCTGTATCCAGAGGCCATTTCTACCCTGTCTGGA
TCTACATTCTGGGCTGTTGTGTTTTTCGTCATGCTCCTGGCGCTGGGCCTTGACAGCTCA
ATGGGAGGCATGGAGGCTGTCATCACGGGCCTGGCAGATGACTTCCAGGTCCTGAAGCGA
CACCGGAAACTCTTCACATTTGGCGTCACCTTCAGCACTTTCCTTCTCGCCCTGTTCTGC
ATAACCAAGGGTGGAATTTACGTCTTGACCCTCCTGGACACCTTTGCTGCGGGCACCTCC
ATCCTTTTTGCTGTCCTCATGGAAGCCATCGGAGTTTCCTGGTTTTATGGAGTGGACAGG
TTCAGCAACGACATCCAGCAGATGATGGGGTTCAGGCCGGGTCTATACTGGAGACTGTGC
TGGAAGTTCGTCAGTCCTGCCTTCCTCCTGTTCGTGGTTGTGGTCAGCATCATCAACTTC
AAGCCACTCACCTACGACGACTACATCTTCCCGCCCTGGGCCAACTGGGTGGGGTGGGGC
ATCGCCCTGTCCTCCATGGTCCTGGTGCCCATCTACGTCATCTATAAGTTCCTCAGCACG
CAGGGCTCTCTTTGGGAGAGACTGGCCTATGGCATCACGCCAGAGAACGAGCACCACCTG
GTGGCTCAGAGGGACATCAGACAGTTCCAGTTGCAACACTGGCTGGCCATCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID SLC6A2 Link Image
Target 1 GenAtlas ID SLC6A2 Link Image
Target 1 HGNC ID HGNC:11048 Link Image
Target 1 Chromosome Location 16
Target 1 Locus 16q12.2
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Shannon JR, Flattem NL, Jordan J, Jacob G, Black BK, Biaggioni I, Blakely RD, Robertson D: Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N Engl J Med. 2000 Feb 24;342(8):541-9. [PubMed Link Image]
  2. Torres GE, Yao WD, Mohn AR, Quan H, Kim KM, Levey AI, Staudinger J, Caron MG: Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron. 2001 Apr;30(1):121-34. [PubMed Link Image]
  3. Pacholczyk T, Blakely RD, Amara SG: Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. Nature. 1991 Mar 28;350(6316):350-4. [PubMed Link Image]
  4. Porzgen P, Bonisch H, Bruss M: Molecular cloning and organization of the coding region of the human norepinephrine transporter gene. Biochem Biophys Res Commun. 1995 Oct 24;215(3):1145-50. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  2. 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 Link Image]
  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 Link Image]
  4. 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 Link Image]
  5. 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 Link Image]
Drug Target 2 [top]
Target 2 ID 713
Target 2 Name Sodium-dependent dopamine transporter
Target 2 Synonyms
  1. DA transporter
  2. DAT
Target 2 Gene Name SLC6A3
Target 2 Protein Sequence >Sodium-dependent dopamine transporter 
MSKSKCSVGLMSSVVAPAKEPNAVGPKEVELILVKEQNGVQLTSSTLTNPRQSPVEAQDR
ETWGKKIDFLLSVIGFAVDLANVWRFPYLCYKNGGGAFLVPYLLFMVIAGMPLFYMELAL
GQFNREGAAGVWKICPILKGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHC
NNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAEYFERGVLHLHQSHGIDDLGPPRWQL
TACLVLVIVLLYFSLWKGVKTSGKVVWITATMPYVVLTALLLRGVTLPGAIDGIRAYLSV
DFYRLCEASVWIDAATQVCFSLGVGFGVLIAFSSYNKFTNNCYRDAIVTTSINSLTSFSS
GFVVFSFLGYMAQKHSVPIGDVAKDGPGLIFIIYPEAIATLPLSSAWAVVFFIMLLTLGI
DSAMGGMESVITGLIDEFQLLHRHRELFTLFIVLATFLLSLFCVTNGGIYVFTLLDHFAA
GTSILFGVLIEAIGVAWFYGVGQFSDDIQQMTGQRPSLYWRLCWKLVSPCFLLFVVVVSI
VTFRPPHYGAYIFPDWANALGWVIATSSMAMVPIYAAYKFCSLPGSFREKLAYAIAPEKD
RELVDRGEVRQFTLRHWLKV
Target 2 Number of Residues 630
Target 2 Molecular Weight 68496
Target 2 Theoretical pI 6.92
Target 2 GO Classification
Function
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity
dopamine:sodium symporter activity
Process
physiological process
cellular physiological process
transport
neurotransmitter transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane
Target 2 General Function Involved in dopamine:sodium symporter activity
Target 2 Specific Function Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 69-89
  • 96-116
  • 140-160
  • 238-256
  • 265-282
  • 318-335
  • 347-368
  • 401-420
  • 447-465
  • 481-501
  • 522-541
  • 560-578
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 553260 Link Image
Target 2 UniProtKB/Swiss-Prot ID Q01959 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name SC6A3_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >1863 bp 
ATGAGTAAGAGCAAATGCTCCGTGGGACTCATGTCTTCCGTGGTGGCCCCGGCTAAGGAG
CCCAATGCCGTGGGCCCGAAGGAGGTGGAGCTCATCCTTGTCAAGGAGCAGAACGGAGTG
CAGCTCACCAGCTCCACCCTCACCAACCCGCGGCAGAGCCCCGTGGAGGCCCAGGATCGG
GAGACCTGGGGCAAGAAGATCGACTTTCTCCTGTCCGTCATTGGCTTTGCTGTGGACCTG
GCCAACGTCTGGCGGTTCCCCTACCTGTGCTACAAAAATGGTGGCGGTGCCTTCCTGGTC
CCCTACCTGCTCTTCATGGTCATTGCTGGGATGCCACTTTTCTACATGGAGCTGGCCCTC
GGCCAGTTCAACAGGGAAGGGGCCGCTGGTGTCTGGAAGATCTGCCCCATACTGAAAGGT
GTGGGCTTCACGGTCATCCTCATCTCACTGTATGTCGGCTTCTTCTACAACGTCATCATC
GCCTGGGCGCTGCACTATCTCTTCTCCTCCTTCACCACGGAGCTCCCCTGGATCCACTGC
AACAACTCCTGGAACAGCCCCAACTGCTCGGATGCCCATCCTGGTGACTCCAGTGGAGAC
AGCTCGGGCCTCAACGACACTTTTGGGACCACACCTGCTGCCGAGTACTTTGAACGTGGC
GTGCTGCACCTCCACCAGAGCCATGGCATCGACGACCTGGGGCCTCCGCGGTGGCAGCTC
ACAGCCTGCCTGGTGCTGGTCATCGTGCTGCTCTACTTCAGCCTCTGGAAGGGCGTGAAG
ACCTCAGGGAAGGTGGTATGGATCACAGCCACCATGCCATACGTGGTCCTCACTGCCCTG
CTCCTGCGTGGGGTCACCCTCCCTGGAGCCATAGACGGCATCAGAGCATACCTGAGCGTT
GACTTCTACCGGCTCTGCGAGGCGTCTGTTTGGATTGACGCGGCCACCCAGGTGTGCTTC
TCCCTGGGCGTGGGGTTCGGGGTGCTGATCGCCTTCTCCAGCTACAACAAGTTCACCAAC
AACTGCTACAGGGACGCGATTGTCACCACCTCCATCAACTCCCTGACGAGCTTCTCCTCC
GGCTTCGTCGTCTTCTCCTTCCTGGGGTACATGGCACAGAAGCACAGTGTGCCCATCGGG
GACGTGGCCAAGGACGGGCCAGGGCTGATCTTCATCATCTACCCGGAAGCCATCGCCACG
CTCCCTCTGTCCTCAGCCTGGGCCGTGGTCTTCTTCATCATGCTGCTCACCCTGGGTATC
GACAGCGCCATGGGTGGTATGGAGTCAGTGATCACCGGGCTCATCGATGAGTTCCAGCTG
CTGCACAGACACCGTGAGCTCTTCACGCTCTTCATCGTCCTGGCGACCTTCCTCCTGTCC
CTGTTCTGCGTCACCAACGGTGGCATCTACGTCTTCACGCTCCTGGACCATTTTGCAGCC
GGCACGTCCATCCTCTTTGGAGTGCTCATCGAAGCCATCGGAGTGGCCTGGTTCTATGGT
GTTGGGCAGTTCAGCGACGACATCCAGCAGATGACCGGGCAGCGGCCCAGCCTGTACTGG
CGGCTGTGCTGGAAGCTGGTCAGCCCCTGCTTTCTCCTGTTCGTGGTCGTGGTCAGCATT
GTGACCTTCAGACCCCCCCACTACGGAGCCTACATCTTCCCCGACTGGGCCAACGCGCTG
GGCTGGGTCATCGCCACATCCTCCATGGCCATGGTGCCCATCTATGCGGCCTACAAGTTC
TGCAGCCTGCCTGGGTCCTTTCGAGAGAAACTGGCCTACGCCATTGCACCCGAGAAGGAC
CGTGAGCTGGTGGACAGAGGGGAGGTGCGCCAGTTCACGCTCCGCCACTGGCTCAAGGTG
TAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID SLC6A3 Link Image
Target 2 GenAtlas ID SLC6A3 Link Image
Target 2 HGNC ID HGNC:11049 Link Image
Target 2 Chromosome Location 5
Target 2 Locus 5p15.3
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Vandenbergh DJ, Thompson MD, Cook EH, Bendahhou E, Nguyen T, Krasowski MD, Zarrabian D, Comings D, Sellers EM, Tyndale RF, George SR, O'Dowd BF, Uhl GR: Human dopamine transporter gene: coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations. Mol Psychiatry. 2000 May;5(3):283-92. [PubMed Link Image]
  3. Greenwood TA, Alexander M, Keck PE, McElroy S, Sadovnick AD, Remick RA, Kelsoe JR: Evidence for linkage disequilibrium between the dopamine transporter and bipolar disorder. Am J Med Genet. 2001 Mar 8;105(2):145-51. [PubMed Link Image]
  4. Torres GE, Yao WD, Mohn AR, Quan H, Kim KM, Levey AI, Staudinger J, Caron MG: Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron. 2001 Apr;30(1):121-34. [PubMed Link Image]
  5. Bannon MJ, Poosch MS, Xia Y, Goebel DJ, Cassin B, Kapatos G: Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7095-9. [PubMed Link Image]
  6. Vandenbergh DJ, Persico AM, Uhl GR: A human dopamine transporter cDNA predicts reduced glycosylation, displays a novel repetitive element and provides racially-dimorphic TaqI RFLPs. Brain Res Mol Brain Res. 1992 Sep;15(1-2):161-6. [PubMed Link Image]
  7. Giros B, el Mestikawy S, Godinot N, Zheng K, Han H, Yang-Feng T, Caron MG: Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. Mol Pharmacol. 1992 Sep;42(3):383-90. [PubMed Link Image]
  8. Donovan DM, Vandenbergh DJ, Perry MP, Bird GS, Ingersoll R, Nanthakumar E, Uhl GR: Human and mouse dopamine transporter genes: conservation of 5'-flanking sequence elements and gene structures. Brain Res Mol Brain Res. 1995 Jun;30(2):327-35. [PubMed Link Image]
  9. Pristupa ZB, Wilson JM, Hoffman BJ, Kish SJ, Niznik HB: Pharmacological heterogeneity of the cloned and native human dopamine transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding. Mol Pharmacol. 1994 Jan;45(1):125-35. [PubMed Link Image]
  10. Kawarai T, Kawakami H, Yamamura Y, Nakamura S: Structure and organization of the gene encoding human dopamine transporter. Gene. 1997 Aug 11;195(1):11-8. [PubMed Link Image]
Target 2 Drug 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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 824
Target 3 Name Sodium-dependent serotonin transporter
Target 3 Synonyms
  1. 5HT transporter
  2. 5HTT
Target 3 Gene Name SLC6A4
Target 3 Protein Sequence >Sodium-dependent serotonin transporter 
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR
HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP
YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM
AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH
RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA
TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD
ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS
TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT
LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC
WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT
PGTFKERIIKSITPETPTEIPCGDIRLNAV
Target 3 Number of Residues 640
Target 3 Molecular Weight 70325
Target 3 Theoretical pI 6.17
Target 3 GO Classification
Function
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity
Process
physiological process
cellular physiological process
transport
neurotransmitter transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane
Target 3 General Function Involved in serotonin:sodium symporter activity
Target 3 Specific Function Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 88-108
  • 116-135
  • 160-180
  • 253-271
  • 280-297
  • 333-350
  • 362-383
  • 417-436
  • 464-482
  • 498-518
  • 539-558
  • 577-595
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 36433 Link Image
Target 3 UniProtKB/Swiss-Prot ID P31645 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name SC6A4_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 3 Gene Sequence >1893 bp 
ATGGAGACGACGCCCTTGAATTCTCAGAAGCAGCTATCAGCGTGTGAAGATGGAGAAGAT
TGTCAGGAAAACGGAGTTCTACAGAAGGTTGTTCCCACCCCAGGGGACAAAGTGGAGTCC
GGGCAAATATCCAATGGGTACTCAGCAGTTCCAAGTCCTGGTGCGGGAGATGACACACGG
CACTCTATCCCAGCGACCACCACCACCCTAGTGGCTGAGCTTCATCAAGGGGAACGGGAG
ACCTGGGGCAAGAAGGTGGATTTCCTTCTCTCAGTGATTGGCTATGCTGTGGACCTGGGC
AATGTCTGGCGCTTCCCCTACATATGTTACCAGAATGGAGGGGGGGCATTCCTCCTCCCC
TACACCATCATGGCCATTTTTGGGGGAATCCCGCTCTTTTACATGGAGCTCGCACTGGGA
CAGTACCACCGAAATGGATGCATTTCAATATGGAGGAAAATCTGCCCGATTTTCAAAGGG
ATTGGTTATGCCATCTGCATCATTGCCTTTTACATTGCTTCCTACTACAACACCATCATG
GCCTGGGCGCTATACTACCTCATCTCCTCCTTCACGGACCAGCTGCCCTGGACCAGCTGC
AAGAACTCCTGGAACACTGGCAACTGCACCAATTACTTCTCCGAGGACAACATCACCTGG
ACCCTCCATTCCACGTCCCCTGCTGAAGAATTTTACACGCGCCACGTCCTGCAGATCCAC
CGGTCTAAGGGGCTCCAGGACCTGGGGGGCATCAGCTGGCAGCTGGCCCTCTGCATCATG
CTGATCTTCACTGTTATCTACTTCAGCATCTGGAAAGGCGTCAAGACCTCTGGCAAGGTG
GTGTGGGTGACAGCCACCTTCCCTTATATCATCCTTTCTGTCCTGCTGGTGAGGGGTGCC
ACCCTCCCTGGAGCCTGGAGGGGTGTTCTCTTCTACTTGAAACCCAATTGGCAGAAACTC
CTGGAGACAGGGGTGTGGATAGATGCAGCCGCTCAGATCTTCTTCTCTCTTGGTCCGGGC
TTTGGGGTCCTGCTGGCTTTTGCTAGCTACAACAAGTTCAACAACAACTGCTACCAAGAT
GCCCTGGTGACCAGCGTGGTGAACTGCATGACGAGCTTCGTTTCGGGATTTGTCATCTTC
ACAGTGCTCGGTTACATGGCTGAGATGAGGAATGAAGATGTGTCTGAGGTGGCCAAAGAC
GCAGGTCCCAGCCTCCTCTTCATCACGTATGCAGAAGCGATAGCCAACATGCCAGCGTCC
ACTTTCTTTGCCATCATCTTCTTTCTGATGTTAATCACGCTGGGCTTGGACAGCACGTTT
GCAGGCTTGGAGGGGGTGATCACGGCTGTGCTGGATGAGTTCCCACACGTCTGGGCCAAG
CGCCGGGAGCGGTTCGTGCTCGCCGTGGTCATCACCTGCTTCTTTGGATCCCTGGTCACC
CTGACTTTTGGAGGGGCCTACGTGGTGAAGCTGCTGGAGGAGTATGCCACGGGGCCCGCA
GTGCTCACTGTCGCGCTGATCGAAGCAGTCGCTGTGTCTTGGTTCTATGGCATCACTCAG
TTCTGCAGGGACGTGAAGGAAATGCTCGGCTTCAGCCCGGGGTGGTTCTGGAGGATCTGC
TGGGTGGCCATCAGCCCTCTGTTTCTCCTGTTCATCATTTGCAGTTTTCTGATGAGCCCG
CCACAACTACGACTTTTCCAATATAATTATCCTTACTGGAGTATCATCTTGGGTTACTGC
ATAGGAACCTCATCTTTCATTTGCATCCCCACATATATAGCTTATCGGTTGATCATCACT
CCAGGGACATTTAAAGAGCGTATTATTAAAAGTATTACCCCGGAGACACCAACAGAAATT
CCTTGTGGGGACATCCGCTTGAATGCTGTGTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID SLC6A4 Link Image
Target 3 GenAtlas ID SLC6A4 Link Image
Target 3 HGNC ID HGNC:11050 Link Image
Target 3 Chromosome Location 17
Target 3 Locus 17q11.1-q12
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R: Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003 Jul 18;301(5631):386-9. [PubMed Link Image]
  3. Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS, Ganapathy V, Blakely RD: Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2542-6. [PubMed Link Image]
  4. Lesch KP, Wolozin BL, Murphy DL, Reiderer P: Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem. 1993 Jun;60(6):2319-22. [PubMed Link Image]
  5. Lesch KP, Wolozin BL, Estler HC, Murphy DL, Riederer P: Isolation of a cDNA encoding the human brain serotonin transporter. J Neural Transm Gen Sect. 1993;91(1):67-72. [PubMed Link Image]
Target 3 Drug 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 Link Image]
  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 Link Image]
  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 Link Image]

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.