Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
 

 

TTD Target ID: TTDS00017

Target Information
NameSodium-dependent dopamine transporter    
Type of targetSuccessful target    
SynonymsDA transporter    
DAT    
Dopamine transporter    
DiseaseParkinson's disease    [1][2]
Drug(s)MethylphenidateApprovedAttention deficit hyperactivity disorder[3]
MethylphenidatePhase IVTraumatic brain injury[4]
RTI-336Phase I completedCocaine addiction[5]
VanoxerineTerminated in Phase ICocaine addiction[5]
BioChemical ClassTransmembrane protein    
PathwayParkinson's disease
UniProt IDQ01959
FunctionAmine transporter, terminating the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.    
SequenceMSKSKCSVGLMSSVVAPAKEPNAVGPKEVELILVKEQNGVQLTSSTLTNPRQSPVEAQDR ETWGKKIDFLLSVIGFAVDLANVWRFPYLCYKNGGGAFLVPYLLFMVIAGMPLFYMELAL GQFNREGAAGVWKICPILKGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHC NNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAEYFERGVLHLHQSHGIDDLGPPRWQL TACLVLVIVLLYFSLWKGVKTSGKVVWITATMPYVVLTALLLRGVTLPGAIDGIRAYLSV DFYRLCEASVWIDAATQVCFSLGVGFGVLIAFSSYNKFTNNCYRDAIVTTSINSLTSFSS GFVVFSFLGYMAQKHSVPIGDVAKDGPGLIFIIYPEAIATLPLSSAWAVVFFIMLLTLGI DSAMGGMESVITGLIDEFQLLHRHRELFTLFIVLATFLLSLFCVTNGGIYVFTLLDHFAA GTSILFGVLIEAIGVAWFYGVGQFSDDIQQMTGQRPSLYWRLCWKLVSPCFLLFVVVVSI VTFRPPHYGAYIFPDWANALGWVIATSSMAMVPIYAAYKFCSLPGSFREKLAYAIAPEKD RELVDRGEVRQFTLRHWLKV
Target ValidationClick to Find Target Validation Information.    
Inhibitor (2R,3R)-iodoreboxetine[6]
(2S,3S)-iodoreboxetine[6]
(R)-DULOXETINE[7]
(R)-Norfluoxetine[8]
(S)-Norfluoxetine[8]
1-benzylpiperidine hydrochloride[9]
10R-hydroxylobel-7-ene[10]
10R-hydroxylobelane[10]
10S-hydroxylobel-7-ene[10]
10S-hydroxylobelane[10]
1S,2R-milnacipran[11]
8R-hydroxylobel-9-ene[12]
8R-hydroxylobelane[10]
8S-hydroxylobel-9-ene[10]
8S-hydroxylobelane[10]
AMINOBENZTROPINE[13]
ANOLOBINE[14]
ANONAINE[14]
ANTIOQUINE[14]
COCAINE.HCL[9]
COCLAURINE[14]
D-166A[15]
D-211A[15]
D-211B[15]
D-254C[15]
D-257A[15]
D-257C[15]
DEXMETHYLPHENIDATE[16]
DEXMETHYLPHENIDATE HYDROCHLORIDE[9]
DIFLUOROBENZTROPINE[17]
DIMETHYLGRISABINE[14]
FLUOXETINE HYDROCHLORIDE[18]
GB-12819[19]
GBR-12909[20]
HOMOAROMOLINE[14]
ISOPILINE[14]
ISOTETRANDRINE[14]
LITOXETINE[21]
METHYLENEDIOXYAMPHETAMINE[22]
METHYLENEDIOXYMETHAMPHETAMINE[23]
N,Ndimethyl milnacipran[24]
N-Benzylmethylphenidate[16]
NISOXETINE[25]
NORBOLDINE[14]
NORSTEPHALAGINE[14]
O-methyldauricine[14]
OBABERINE[14]
PF-18298,   PF-184298[26]
PF-3409409[27]
PF-526014[26]
PSEUDOCOCAINE[28]
PYROVALERONE[29]
R-226161[30]
R-NORDULOXETINE[31]
RTI-219[32]
SECOCULARIDINE[14]
WIN-35065[32]
WIN-35065-2[33]
WIN-35066-2[34]
WIN_35428[33]
methyl 2- (naphthalen-2-yl)benzoate[35]
para-chloroamphetamine[23]
Antagonist4-Methoxyamphetamine[36]
BlockerMethylphenidate[3]
Methylphenidate[4]
RTI-336[5]
Vanoxerine[5]
Modulator3,4-Methylenedioxymethamphetamine[37]
MMDA[38]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1The dopamine transporter: importance in Parkinson's disease. Ann Neurol. 2004 Jun;55(6):766-73. To Reference
Ref 2Dopamine transporter function assessed by antisense knockdown in the rat: protection from dopamine neurotoxicity. Synapse. 2000 Sep 1;37(3):171-8. To Reference
Ref 3Imaging the effects of methylphenidate on brain dopamine: new model on its therapeutic actions for attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005 Jun 1;57(11):1410-5. Epub 2005 Jan 12. To Reference
Ref 4Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84. To Reference
Ref 5Emerging pharmacological strategies in the fight against cocaine addiction. Expert Opin Emerg Drugs. 2006 Mar;11(1):91-8. To Reference
Ref 6Bioorg Med Chem Lett. 2008 Sep 15;18(18):4940-3. Epub 2008 Aug 19.New iodoreboxetine analogues for SPECT imaging of the noradrenaline transporter. To Reference
Ref 7Bioorg Med Chem Lett. 2009 Jan 1;19(1):58-61. Epub 2008 Nov 13.1-Naphthyl and 4-indolyl arylalkylamines as selective monoamine reuptake inhibitors. To Reference
Ref 8Bioorg Med Chem. 2009 Jan 1;17(1):337-43. Epub 2008 Nov 5.Stereoselective inhibition of serotonin re-uptake and phosphodiesterase by dual inhibitors as potential agents for depression. To Reference
Ref 9J Med Chem. 2007 May 31;50(11):2718-31. Epub 2007 May 10.Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate. To Reference
Ref 10Bioorg Med Chem Lett. 2006 Oct 1;16(19):5018-21. Epub 2006 Aug 14.Des-keto lobeline analogs with increased potency and selectivity at dopamine and serotonin transporters. To Reference
Ref 11J Med Chem. 2008 Nov 27;51(22):7265-72.Characterization of thien-2-yl 1S,2R-milnacipran analogues as potent norepinephrine/serotonin transporter inhibitors for the treatment of neuropathic pain. To Reference
Ref 12Bioorg Med Chem. 2010 Jan 15;18(2):640-9. Epub 2009 Dec 6.Lobeline esters as novel ligands for neuronal nicotinic acetylcholine receptors and neurotransmitter transporters. To Reference
Ref 13J Med Chem. 1997 Mar 14;40(6):851-7.3'-Chloro-3 alpha-(diphenylmethoxy)tropane but not 4'-chloro-3 alpha-(diphenylmethoxy)tropane produces a cocaine-like behavioral profile. To Reference
Ref 14J. Nat. Prod. 58(10):1475-1484 (1995) To Reference
Ref 15Bioorg Med Chem. 2008 Mar 15;16(6):2769-78. Epub 2008 Jan 11.Further structural optimization of cis-(6-benzhydryl-piperidin-3-yl)-benzylamine and 1,4-diazabicyclo[3.3.1]nonane derivatives by introducing an exocyclic hydroxyl group: interaction with dopamine, serotonin, and norepinephrine transporters. To Reference
Ref 16Bioorg Med Chem. 2010 Oct 15;18(20):7221-38. Epub 2010 Aug 19.Quantitative structure-activity relationship studies of threo-methylphenidate analogs. To Reference
Ref 17J Med Chem. 2006 Oct 19;49(21):6391-9.Structure-activity relationship studies on a novel series of (S)-2beta-substituted 3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogues for in vivo investigation. To Reference
Ref 18Bioorg Med Chem. 2010 Dec 1;18(23):8356-64. Epub 2010 Sep 29.Synthesis and structure-activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands. To Reference
Ref 19Bioorg Med Chem Lett. 2002 Sep 2;12(17):2387-90.Synthesis and dopamine transporter binding affinities of 3alpha-benzyl-8-(diarylmethoxyethyl)-8-azabicyclo[3.2.1]octanes. To Reference
Ref 20Bioorg Med Chem Lett. 2008 Oct 1;18(19):5238-41. Epub 2008 Aug 22.Dual DAT/sigma1 receptor ligands based on 3-(4-(3-(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-1-phenylpropan-1-ol. To Reference
Ref 21Bioorg Med Chem Lett. 2009 Oct 15;19(20):5893-7. Epub 2009 Aug 21.Design and optimisation of selective serotonin re-uptake inhibitors with high synthetic accessibility: part 2. To Reference
Ref 22Bioorg Med Chem. 2010 Jun 1;18(11):4009-31. Epub 2010 Apr 13.Synthesis and in vitro toxicity of 4-MTA, its characteristic clandestine synthesis byproducts and related sulfur substituted alpha-alkylthioamphetamines. To Reference
Ref 23Eur J Med Chem. 2009 Dec;44(12):4862-88. Epub 2009 Aug 6.Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents. To Reference
Ref 24Bioorg Med Chem Lett. 2008 Feb 15;18(4):1346-9. Epub 2008 Jan 9.Studies on the SAR and pharmacophore of milnacipran derivatives as monoamine transporter inhibitors. To Reference
Ref 25Bioorg Med Chem Lett. 2008 Jul 15;18(14):4224-7. Epub 2008 May 20.Discovery of a potent, selective, and less flexible selective norepinephrine reuptake inhibitor (sNRI). To Reference
Ref 26Bioorg Med Chem Lett. 2010 Jun 15;20(12):3788-92. Epub 2010 Apr 18.Second generation N-(1,2-diphenylethyl)piperazines as dual serotonin and noradrenaline reuptake inhibitors: improving metabolic stability and reducing ion channel activity. To Reference
Ref 27Bioorg Med Chem Lett. 2009 Aug 15;19(16):4579-83. Epub 2009 Jul 2.Design, synthesis and evaluation of N-[(3S)-pyrrolidin-3-yl]benzamides as selective noradrenaline reuptake inhibitors: CNS penetration in a more polar template. To Reference
Ref 28Bioorg Med Chem Lett. 1999 Jul 5;9(13):1831-6.Synthesis of 8-Oxa analogues of norcocaine endowed with interesting cocaine-like activity. To Reference
Ref 29Bioorg Med Chem. 2009 Jun 1;17(11):3770-4. Epub 2009 May 3.A novel photoaffinity ligand for the dopamine transporter based on pyrovalerone. To Reference
Ref 30Bioorg Med Chem. 2007 Jun 1;15(11):3649-60. Epub 2007 Mar 21.Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism. To Reference
Ref 31Bioorg Med Chem. 2009 Oct 1;17(19):6890-7. Epub 2009 Aug 20.Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression. To Reference
Ref 32J Med Chem. 2007 Jul 26;50(15):3686-95. Epub 2007 Jun 30.Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3beta-[4-methylphenyl and 4-chlorophenyl]-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes. To Reference
Ref 33J Med Chem. 1996 Oct 11;39(21):4139-41.3 alpha-(4'-substituted phenyl)tropane-2 beta-carboxylic acid methyl esters: novel ligands with high affinity and selectivity at the dopamine transporter. To Reference
Ref 34J Med Chem. 2004 Dec 2;47(25):6401-9.Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers. To Reference
Ref 35Bioorg Med Chem. 2007 Jun 15;15(12):4159-74. Epub 2007 Mar 30.Synthesis, inhibition and binding of simple non-nitrogen inhibitors of monoamine transporters. To Reference
Ref 36Daws LC, Irvine RJ, Callaghan PD, Toop NP, White JM, Bochner F: Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat. Prog Neuropsychopharmacol Biol Psychiatry. 2000 Aug;24(6):955-77. To Reference
Ref 37Freudenmann RW, Oxler F, Bernschneider-Reif S: The origin of MDMA (ecstasy) revisited: the true story reconstructed from the original documents. Addiction. 2006 Sep;101(9):1241-5. To Reference
Ref 38Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference



 

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