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Showing toxin card for Methylphenidate (T3D2786)

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Version 1.0
Creation Date 2009-07-21 20:26:52
Update Date 2010-05-18 20:59:54
Accession Number T3D2786
Name Methylphenidate
Compound Type
  • Adrenergic Agent
  • Adrenergic Uptake Inhibitor
  • Central Nervous System Stimulant
  • Dopamine Uptake Inhibitor
  • Drug
  • Sympathomimetic
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. d-methylphenidate HCl
  2. Methyl phenidyl acetate
  3. methylphenidate
  4. Methylphenidate HCl
  5. Methylphenidate hydrochloride
  6. Methylphenidatum [INN-Latin]
  7. Methylphenidylacetate hydrochloride
  8. Metilfenidat hydrochloride
  9. Metilfenidato [INN-Spanish]
  10. Metilfenidato [Italian]
  11. Phenidylate
Chemical IUPAC Name methyl 2-phenyl-2-(piperidin-2-yl)acetate
Chemical Formula C14H19NO2
Chemical Structure Structure
CAS Registry Number 113-45-1
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 Key InChIKey=DUGOZIWVEXMGBE-UHFFFAOYSA-N
PubChem Compound ID 4158 Link Image
KEGG ID C07196 Link Image
UniProt ID Not Available
OMIM ID Not Available
ChEBI ID 6887 Link Image
BioCyc ID Not Available
SuperToxic ID Not Available
CTD ID Not Available
Stitch ID Methylphenidate Link Image
DrugBank ID DB00422 Link Image
PDB ID Not Available
ACToR ID Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Methylphenidate Link Image
Monoisotopic Mass 233.141579
MOL File Show
PDB File Show
SDF File Show
SMILES COC(=O)C(C1CCCCN1)C1=CC=CC=C1
Appearance Not Available
Melting Point 224-226oC
Solubility 1255mg/L
Predicted LogP 2.2549
Route of Exposure Oral
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.
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.
Toxicity Values LD50: 190 mg/kg (oral, mice)
Lethal Dose Not Available
Carcinogenicity (IARC Classification) Not Available
Uses/Sources Not Available
Minimum Risk Level Not Available
Health Effects Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.
Symptoms 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.
Treatment Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. Gastric contents may be evacuated by gastric lavage. In the presence of severe intoxication, use a carefully titrated dosage of a short-acting barbiturate before performing gastric lavage. Other measures to detoxify the gut include administration of activated charcoal and a cathartic. Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required for hyperpyrexia. (V650)
General References
  • T748 - Keating GM, McClellan K, Jarvis B: Methylphenidate (OROS formulation). CNS Drugs. 2001;15(6):495-500; discussion 501-3. [PubMed Link Image]
  • T750 - Sharma RP, Javaid JI, Pandey GN, Easton M, Davis JM: Pharmacological effects of methylphenidate on plasma homovalic acid and growth hormone. Psychiatry Res. 1990 Apr;32(1):9-17. [PubMed Link Image]
  • T749 - 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]
  • T205 - 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]
  • T751 - 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]
  • T747 - Drugs.com
Targets
  1. Sodium-dependent dopamine transporter
  2. Sodium-dependent noradrenaline transporter
  3. Sodium-dependent serotonin transporter
Target 1 [top]
Target 1 ID 1144
Target 1 Name Sodium-dependent dopamine transporter
Target 1 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.
Target 1 Description Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 1 Synonyms
  1. DA transporter; DAT; Solute carrier family 6 member 3
Target 1 Gene Name SLC6A3
Target 1 Protein Sequence >Sodium-dependent dopamine transporter 
MSKSKCSVGLMSSVVAPAKEPNAVGPKEVELILVKEQNGVQLTSSTLTNPRQSPVEAQDR
ETWGKKIDFLLSVIGFAVDLANVWRFPYLCYKNGGGAFLVPYLLFMVIAGMPLFYMELAL
GQFNREGAAGVWKICPILKGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHC
NNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAEYFERGVLHLHQSHGIDDLGPPRWQL
TACLVLVIVLLYFSLWKGVKTSGKVVWITATMPYVVLTALLLRGVTLPGAIDGIRAYLSV
DFYRLCEASVWIDAATQVCFSLGVGFGVLIAFSSYNKFTNNCYRDAIVTTSINSLTSFSS
GFVVFSFLGYMAQKHSVPIGDVAKDGPGLIFIIYPEAIATLPLSSAWAVVFFIMLLTLGI
DSAMGGMESVITGLIDEFQLLHRHRELFTLFIVLATFLLSLFCVTNGGIYVFTLLDHFAA
GTSILFGVLIEAIGVAWFYGVGQFSDDIQQMTGQRPSLYWRLCWKLVSPCFLLFVVVVSI
VTFRPPHYGAYIFPDWANALGWVIATSSMAMVPIYAAYKFCSLPGSFREKLAYAIAPEKD
RELVDRGEVRQFTLRHWLKV
Target 1 Number of Residues 620
Target 1 Molecular Weight 68494.3
Target 1 Theoretical pI 6.92
Target 1 GO Classification
Function
dopamine:sodium symporter activity
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 dopamine:sodium symporter activity
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Signals
  • None
Target 1 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 1 Essentiality Non Essential
Target 1 Domain Function PF00209:SNF
Target 1 GenBank ID Protein Not Available
Target 1 UniProtKB ID Q01959 Link Image
Target 1 Cellular Location Membrane
Target 1 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 1 GenBank Gene ID Not Available
Target 1 GeneCard ID SLC6A3 Link Image
Target 1 GenAtlas ID SLC6A3 Link Image
Target 1 HGNC ID HGNC:11049 Link Image
Target 1 Chromosome Location Not Available
Target 1 Locus 5p15.3
Target 1 SNPs SNPJam Report Link Image
Target 1 Toxin References
  • T760 - 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]
  • S918 - Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  • T762 - 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]
  • T758 - 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]
  • T761 - 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]
  • T757 - 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]
Target 1 General References 1359373; 1406597; 8302271; 9300814; 10889531; 11304827; 7637582; 1353885; 11343649
Target 2 [top]
Target 2 ID 1152
Target 2 Name Sodium-dependent noradrenaline transporter
Target 2 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.
Target 2 Description Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 2 Synonyms
  1. Norepinephrine transporter; NET; Solute carrier family 6 member 2
Target 2 Gene Name SLC6A2
Target 2 Protein Sequence >Sodium-dependent noradrenaline transporter 
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWG
KKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYN
REGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTW
NSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLC
LMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFY
RLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFA
IFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSS
MGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTS
ILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINF
KPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHL
VAQRDIRQFQLQHWLAI
Target 2 Number of Residues 617
Target 2 Molecular Weight 69331.4
Target 2 Theoretical pI 7.53
Target 2 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 2 General Function Involved in norephinephrine:sodium symporter activity
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Signals
  • None
Target 2 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 2 Essentiality Non Essential
Target 2 Domain Function PF00209:SNF
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB ID P23975 Link Image
Target 2 Cellular Location Membrane
Target 2 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 2 GenBank Gene ID Not Available
Target 2 GeneCard ID SLC6A2 Link Image
Target 2 GenAtlas ID SLC6A2 Link Image
Target 2 HGNC ID HGNC:11048 Link Image
Target 2 Chromosome Location Chromosome:16
Target 2 Locus 16q12.2
Target 2 SNPs SNPJam Report Link Image
Target 2 Toxin References
  • T752 - 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]
  • T756 - 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]
  • T755 - 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 juvee rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress. J Neurosci. 2007 Jul 4;27(27):7196-207. [PubMed Link Image]
  • T753 - 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]
  • T754 - 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]
Target 2 General References 2008212; 7488042; 11343649; 10684912
Target 3 [top]
Target 3 ID 1141
Target 3 Name Sodium-dependent serotonin transporter
Target 3 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.
Target 3 Description Terminates the action of serotonin by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 3 Synonyms
  1. 5HT transporter; 5HTT; Solute carrier family 6 member 4
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 630
Target 3 Molecular Weight 70324.2
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 protein binding
Target 3 Pathways Not Available
Target 3 Reactions Not Available
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 Domain Function PF03491:5HT_transporter PF00209:SNF
Target 3 GenBank ID Protein Not Available
Target 3 UniProtKB ID P31645 Link Image
Target 3 Cellular Location Membrane
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 Not Available
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 Chromosome:17
Target 3 Locus 17q11.1-q12
Target 3 SNPs SNPJam Report Link Image
Target 3 Toxin References
  • T759 - 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]
  • T758 - 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]
  • T757 - 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]
Target 3 General References 8452685; 7681602; 7684072; 15489334; 16803896; 10391209; 14593431; 12869649

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.