Target Information

Target General Infomation
Target ID
T22118
Former ID
TTDS00011
Target Name
Dopamine D1 receptor
Gene Name
DRD1
Synonyms
D(1) dopamine receptor; D(1A) dopamine receptor; DRD1
Target Type
Successful
Disease Allergy [ICD9: 995.3; ICD10: T78.4]
Cocaine addiction [ICD9: 304.2; ICD10: F14.2]
Cognitive disorders [ICD9: 290-294, 294.0, 780.09, 780.9, 780.93; ICD10: F01-F07, F04, F05, R41.3]
Dementia [ICD9: 290-294; ICD10: F01-F07]
Excessive bleeding following childbirth and spontaneous or elective abortion [ICD10: O04]
Glaucoma [ICD9: 365; ICD10: H40-H42]
Hypertension [ICD9: 401; ICD10: I10-I16]
Psychiatric disorder [ICD9: 290-319; ICD10: F01-F99]
Parkinson's disease [ICD9: 332; ICD10: G20]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Psychotic disorders [ICD9: 290-299; ICD10: F20-F29]
Sexual dysfunction [ICD9: 302.7; ICD10: F52]
Substance dependence [ICD10: F10-F19]
Schizophrenia [ICD9: 295; ICD10: F20]
Type 2 diabetes [ICD9: 250; ICD10: E11]
Unspecified [ICD code not available]
Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
BioChemical Class
GPCR rhodopsin
Target Validation
T22118
UniProt ID
P21728
Sequence
MRTLNTSAMDGTGLVVERDFSVRILTACFLSLLILSTLLGNTLVCAAVIRFRHLRSKVTN
FFVISLAVSDLLVAVLVMPWKAVAEIAGFWPFGSFCNIWVAFDIMCSTASILNLCVISVD
RYWAISSPFRYERKMTPKAAFILISVAWTLSVLISFIPVQLSWHKAKPTSPSDGNATSLA
ETIDNCDSSLSRTYAISSSVISFYIPVAIMIVTYTRIYRIAQKQIRRIAALERAAVHAKN
CQTTTGNGKPVECSQPESSFKMSFKRETKVLKTLSVIMGVFVCCWLPFFILNCILPFCGS
GETQPFCIDSNTFDVFVWFGWANSSLNPIIYAFNADFRKAFSTLLGCYRLCPATNNAIET
VSINNNGAAMFSSHHEPRGSISKECNLVYLIPHAVGSSEDLKKEEAAGIARPLEKLSPAL
SVILDYDTDVSLEKIQPITQNGQHPT
Drugs and Mode of Action
Drug(s) Fenoldopam Drug Info Approved Hypertension [536361], [543348]
Methylergonovine Drug Info Approved Excessive bleeding following childbirth and spontaneous or elective abortion [551871]
Pergolide Drug Info Approved Parkinson's disease [468029], [536285]
Phenyltoloxamine Drug Info Approved Allergy [551871]
Ecopipam Drug Info Phase 3 Cocaine addiction [524163], [540266]
Zicronapine Drug Info Phase 3 Schizophrenia [523357]
DAS-431 IV Drug Info Phase 2 Dementia [551849]
Intranasal apomorphine Drug Info Phase 2 Sexual dysfunction [527086]
Dihydrexidine Drug Info Phase 1/2 Psychotic disorders [532900]
BSF-78438 Drug Info Preclinical Schizophrenia [536463]
D1 agonist D2 antagonist Drug Info Preclinical Schizophrenia [536463]
ADROGOLIDE HYDROCHLORIDE Drug Info Discontinued in Phase 2 Cognitive disorders [546145]
ADX-10061 Drug Info Discontinued in Phase 2 Psychotic disorders [544910]
BAM-1110 Drug Info Discontinued in Phase 2 Parkinson's disease [545888]
CY-208243 Drug Info Discontinued in Phase 2 Pain [528994]
ZELANDOPAM HYDROCHLORIDE Drug Info Discontinued in Phase 2 Hypertension [545254]
Berupipam Drug Info Discontinued in Phase 1 Psychotic disorders [545634]
BTS-73947 Drug Info Discontinued in Phase 1 Psychotic disorders [546424]
Odapipam Drug Info Discontinued in Phase 1 Psychotic disorders [546051]
SDZ-GLC-756 Drug Info Discontinued in Phase 1 Glaucoma [546521]
A 77636 Drug Info Terminated Parkinson's disease [545188]
A-68930 Drug Info Terminated Hypertension [541323], [545191]
A-69024 Drug Info Terminated Psychotic disorders [545268]
BIMG80 Drug Info Terminated Psychotic disorders [546146]
CEE-03-320 Drug Info Terminated Substance dependence [546271]
NNC-22-0031 Drug Info Terminated Psychotic disorders [534327]
Org-10490 Drug Info Terminated Psychotic disorders [551630]
SDZ-PSD-958 Drug Info Terminated Psychiatric disorder [546576]
SKF 38393 Drug Info Terminated Type 2 diabetes [525668], [543309]
SKF-81297 Drug Info Terminated Parkinson's disease [543311], [545672]
Inhibitor (+)-(1R,1'S)-berbamunine hydrochloride Drug Info [551356]
(+)-(1R,1'S)-thaligrisine hydrochloride Drug Info [551356]
(+)-BUTACLAMOL Drug Info [525773]
(+/-)-nantenine Drug Info [530558]
(-)-(1S,1'R)-O,O-dimethylgrisbine hydrochloride Drug Info [551356]
(R)-(+)-coclaurine Drug Info [534656]
(R)-(-)-10-methyl-11-hydroxyaporphine Drug Info [528876]
(R)-(-)-11-hydroxy-N-n-propylnoraporphine Drug Info [529289]
(R)-(-)-2-methoxy-11-hydroxyaporphine Drug Info [529289]
(R)-(-)-2-methoxy-N-npropylnorapomorphine Drug Info [529289]
(R)-(-)-N-ethyl-2-methoxy-11-hydroxynoraporphine Drug Info [529289]
(R)-(-)-N-propyl-2-methoxy-11-hydroxynoraporphine Drug Info [529289]
(R)-11-Amino-2-methoxyaporphine Drug Info [529541]
(R)-2,11-Diaminoaporphine Drug Info [529541]
(R,S)-homoaromaline hydrochloride Drug Info [551356]
(S)-BULBOCAPNINE Drug Info [528616]
(S)APOMORPHINE Drug Info [530342]
(S,S)-oxandrine hydrochloride Drug Info [551356]
1,2,3,7,12,12a-hexahydro-1-aza-pleiaden-5-ol Drug Info [528616]
1,2,3,7,12,12a-hexahydro-1-aza-pleiadene-5,6-diol Drug Info [528616]
1,2-Bis-[R-(-)-apomorphine-2'-oxy]ethane Drug Info [529349]
1-(4-(1H-pyrazol-1-yl)benzyl)-4-phenylpiperazine Drug Info [528099]
1-Aminomethyl-3-cyclohexyl-isochroman-5,6-diol Drug Info [529371]
1-Aminomethyl-3-phenyl-isochroman-5,6-diol Drug Info [530404]
1-Aminomethyl-isochroman-5,6-diol Drug Info [530404]
1-Benzyl-4-(2-ethynyl-pyrrol-1-yl)-piperidine Drug Info [525629]
1-Benzyl-4-(2-iodo-pyrrol-1-yl)-piperidine Drug Info [525629]
1-Benzyl-4-(2-oxazol-5-yl-pyrrol-1-yl)-piperidine Drug Info [525629]
1-Dibenzo[b,f]oxepin-10-yl-4-methyl-piperazine Drug Info [533570]
1-[2-(2-Benzyl-phenoxy)-ethyl]-piperidine Drug Info [527160]
1-[2-(2-Benzyl-phenoxy)-ethyl]-pyrrolidine Drug Info [527160]
1-[3-(2-Benzyl-phenoxy)-propyl]-pyrrolidine Drug Info [527160]
11-Butyryloxy-N-n-propylnoraporphine Drug Info [529686]
11-Heptanoyloxy-N-n-propylnoraporphine Drug Info [529686]
11-Hexanoyloxy-N-n-propylnoraporphine Drug Info [529686]
11-Propionyloxy-N-n-propylnoraporphine Drug Info [529686]
11-valeryloxynoraporphine Drug Info [529686]
2-methoxyapomorphine Drug Info [529349]
2-Methyl-8-phenyl-1,2,3,4-tetrahydro-isoquinoline Drug Info [533578]
2-{[R-(-)-Apomorphine-2'-oxy]ethoxy}-ethanol Drug Info [529349]
3,8-dibromoboldine Drug Info [525759]
3-bromoboldine Drug Info [525759]
3-Chloroboldine Drug Info [525759]
3-Iodoboldine Drug Info [525759]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one Drug Info [531079]
4-[2-(2-Benzyl-phenoxy)-ethyl]-morpholine Drug Info [527160]
5-(2-Amino-ethyl)-2-chloro-phenol hydrobromide Drug Info [526782]
6-(2-Amino-ethyl)-biphenyl-2,3,4'-triol Drug Info [533481]
6-(2-Amino-ethyl)-biphenyl-2,3-diol Drug Info [533481]
6-(2-Dipropylamino-ethyl)-biphenyl-2,3,4'-triol Drug Info [533481]
6-(2-Dipropylamino-ethyl)-biphenyl-2,3-diol Drug Info [533481]
9-Aminomethyl-9H-fluorene-2,5,6-triol Drug Info [533481]
9-Aminomethyl-9H-fluorene-3,4-diol Drug Info [533481]
A-70108 Drug Info [530404]
BOLDINE Drug Info [525759]
Dihydrexidine Drug Info [528571]
Etoloxamine Drug Info [527160]
FALCARINDIOL Drug Info [529238]
FLUMEZAPINE Drug Info [533515]
FLUTROLINE Drug Info [533512]
GLAUCINE Drug Info [528616]
IBZM Drug Info [529011]
ISOCLOZAPINE Drug Info [534532]
ISOLOXAPINE Drug Info [533577]
MCL-516 Drug Info [529850]
MELOSMINE Drug Info [528616]
N-(4-Dipropylaminobutyl)-4-biphenylcarboxamide Drug Info [529734]
N-(4-Propylaminobutyl)-4-biphenylcarboxamide Drug Info [529734]
NORSTEPHALAGINE Drug Info [528616]
Phenyltoloxamine Drug Info [527160]
PUKATEINE Drug Info [528616]
QUINPIROLE Drug Info [527714]
R-N-PROPYLNORAPOMORPHINE Drug Info [529289]
Ro-21-7767 Drug Info [533759]
SB-271046 Drug Info [529191]
SCH-12679 Drug Info [534738]
SCH-24518 Drug Info [533416]
SK&F-89626 Drug Info [530341]
STEPHOLIDINE Drug Info [530374]
TEPA (possesses cytotoxic activity) Drug Info [534719]
[R-(-)-Apomorphine-2-yl]-(2'-hydroxy-ethyl)ether Drug Info [529349]
Agonist (+)-ADTN Drug Info [529311]
ADROGOLIDE HYDROCHLORIDE Drug Info [526175], [551871]
CY-208243 Drug Info [533392]
D1 agonist D2 antagonist Drug Info [536463]
DAS-431 IV Drug Info [526175]
Fenoldopam Drug Info [536760]
Intranasal apomorphine Drug Info [534197]
N-propylnorapomorphine Drug Info [529311]
SKF-75670 Drug Info [530363]
SKF-83959 Drug Info [533137]
Modulator A 77636 Drug Info
A-68930 Drug Info [526771]
A-69024 Drug Info [526304]
BAM-1110 Drug Info
BIMG80 Drug Info [534408]
CEE-03-320 Drug Info [546272]
Ecopipam Drug Info
ecopipam (controlled-release, Lesch Nyhan syndrome/Tourette's syndrome/compulsive gambling). Psyadon Pharmaceuticals Drug Info
NNC-22-0031 Drug Info [534327]
Org-10490 Drug Info [556264]
Pergolide Drug Info [556264]
SDZ-GLC-756 Drug Info [534322]
SDZ-PSD-958 Drug Info [534179]
SKF 38393 Drug Info [525668]
SKF-81297 Drug Info [533794]
Zicronapine Drug Info [549861]
Antagonist ADX-10061 Drug Info [544911]
Berupipam Drug Info [533594]
BTS-73947 Drug Info [546425], [551871]
Methylergonovine Drug Info [536092]
Odapipam Drug Info [525486]
SCH-23390 Drug Info [537186]
SKF-83556 Drug Info [529311]
ZELANDOPAM HYDROCHLORIDE Drug Info [527452], [551871]
[125I]SCH23982 Drug Info [531411]
[3H]SCH-23390 Drug Info [531521]
Binder BSF-78438 Drug Info [536463]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Calcium signaling pathway
cAMP signaling pathway
Neuroactive ligand-receptor interaction
Gap junction
Dopaminergic synapse
Parkinson&#039
s disease
Cocaine addiction
Amphetamine addiction
Morphine addiction
Alcoholism
PANTHER Pathway Dopamine receptor mediated signaling pathway
PathWhiz Pathway Dopamine Activation of Neurological Reward System
Reactome Dopamine receptors
G alpha (s) signalling events
WikiPathways Hypothetical Network for Drug Addiction
Monoamine GPCRs
GPCRs, Class A Rhodopsin-like
Genes and (Common) Pathways Underlying Drug Addiction
GPCR ligand binding
GPCR downstream signaling
References
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Ref 523357ClinicalTrials.gov (NCT01295372) Safety and Efficacy of Zicronapine in Patients With Schizophrenia. U.S. National Institutes of Health.
Ref 524163ClinicalTrials.gov (NCT01751802) Ecopipam Treatment of Self-Injurious Behavior in Subjects With Lesch-Nyhan Disease. U.S. National Institutes of Health.
Ref 525668The D1 dopamine receptor agonist SKF-38393 stimulates the release of glutamate in the hippocampus. Neuroscience. 1999;94(4):1063-70.
Ref 527086Intranasal apomorphine. Nastech Pharmaceutical. IDrugs. 2004 May;7(5):483-8.
Ref 528994Decrease of behavioral and biochemical denervation supersensitivity of rat striatum by nigral transplants. Neuroscience. 1991;44(1):75-83.
Ref 532900Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder. Neuropsychopharmacology. 2015 Jan;40(2):446-53.
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Ref 541323(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6077).
Ref 543309(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 935).
Ref 543311(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 938).
Ref 543348(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 985).
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Ref 546424Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008043)
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Ref 546576Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009027)
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Ref 525759J Nat Prod. 2000 Apr;63(4):480-4.Halogenated boldine derivatives with enhanced monoamine receptor selectivity.
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Ref 526782J Med Chem. 1992 Nov 13;35(23):4408-14.Synthesis and pharmacological characterization of 2-(4-chloro-3-hydroxyphenyl)ethylamine and N,N-dialkyl derivatives as dopamine receptor ligands.
Ref 527160J Med Chem. 2004 Aug 12;47(17):4155-8.Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 receptor selectivity.
Ref 527452Effect of zelandopam, a dopamine D1-like receptor agonist, in puromycin aminonucleoside nephrosis rats. Eur J Pharmacol. 2005 Mar 7;510(1-2):121-6.
Ref 527714J Med Chem. 2005 Sep 8;48(18):5771-9.Pharmacophore-guided drug discovery investigations leading to bioactive 5-aminotetrahydropyrazolopyridines. Implications for the binding mode of heterocyclic dopamine D3 receptor agonists.
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Ref 528571J Med Chem. 2006 Nov 16;49(23):6848-57.trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline: synthesis, resolution, and preliminary pharmacological characterization of a new dopamine D1 receptor full agonist.
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Ref 528876Bioorg Med Chem Lett. 2007 Aug 1;17(15):4128-30. Epub 2007 May 23.R-(-)-N-alkyl-11-hydroxy-10-hydroxymethyl- and 10-methyl-aporphines as 5-HT1A receptor ligands.
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Ref 529191Bioorg Med Chem Lett. 2008 Jan 15;18(2):738-43. Epub 2007 Nov 17.Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective 5-HT6 receptor antagonists.
Ref 529238Bioorg Med Chem. 2008 Mar 15;16(6):3218-23. Epub 2007 Dec 31.Novel coumarin glycoside and phenethyl vanillate from Notopterygium forbesii and their binding affinities for opioid and dopamine receptors.
Ref 529289J Med Chem. 2008 Feb 28;51(4):983-7. Epub 2008 Feb 6.Synthesis and dopamine receptor affinities of N-alkyl-11-hydroxy-2-methoxynoraporphines: N-alkyl substituents determine D1 versus D2 receptor selectivity.
Ref 529311Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 1991 Apr 18;350(6319):614-9.
Ref 529349Bioorg Med Chem. 2008 Apr 15;16(8):4563-8. Epub 2008 Feb 15.Synthesis and neuropharmacological characterization of 2-O-substituted apomorphines.
Ref 529371J Med Chem. 1991 Oct;34(10):2946-53.Synthesis and pharmacological evaluation of 1-(aminomethyl)-3,4-dihydro-5-hydroxy-1H-2-benzopyrans as dopamine D1 selective ligands.
Ref 529541Bioorg Med Chem. 2008 Jul 15;16(14):6675-81. Epub 2008 Jun 5.Synthesis and pharmacological investigation of novel 2-aminothiazole-privileged aporphines.
Ref 529686Bioorg Med Chem. 2008 Sep 15;16(18):8335-8. Epub 2008 Aug 28.N-Propylnoraporphin-11-O-yl carboxylic esters as potent dopamine D(2) and serotonin 5-HT(1A) receptor dual ligands.
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Ref 529850Bioorg Med Chem Lett. 2009 Jan 1;19(1):51-3. Epub 2008 Nov 13.Synthesis and neuropharmacological evaluation of esters of R(-)-N-alkyl-11-hydroxy-2-methoxynoraporphines.
Ref 530341J Med Chem. 1990 Jun;33(6):1756-64.trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine: a highly potent selective dopamine D1 full agonist.
Ref 530342J Med Chem. 1990 Jun;33(6):1800-5.Synthesis and dopamine receptor affinities of enantiomers of 2-substituted apomorphines and their N-n-propyl analogues.
Ref 530363Dopamine receptor agonists: selectivity and dopamine D1 receptor efficacy. Eur J Pharmacol. 1990 Jun 12;188(6):335-47.
Ref 530374Bioorg Med Chem. 2009 Oct 1;17(19):6898-907. Epub 2009 Aug 20.Dibenzazecine scaffold rebuilding--is the flexibility always essential for high dopamine receptor affinities?.
Ref 530404J Med Chem. 1990 Nov;33(11):2948-50.(1R,3S)-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-3-phenyl-1H-2-benzopyran: a potent and selective D1 agonist.
Ref 530558Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine.
Ref 531079J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential.
Ref 531411Molecular cloning and expression of the gene for a human D1 dopamine receptor. Nature. 1990 Sep 6;347(6288):72-6.
Ref 531521Cloning and expression of human and rat D1 dopamine receptors. Nature. 1990 Sep 6;347(6288):76-80.
Ref 533137Identification of G protein-biased agonists that fail to recruit beta-arrestin or promote internalization of the D1 dopamine receptor. ACS Chem Neurosci. 2015 Apr 15;6(4):681-92.
Ref 533392The D-1 dopamine receptor partial agonist, CY 208-243, exhibits antiparkinsonian activity in the MPTP-treated marmoset. Eur J Pharmacol. 1988 Nov 1;156(2):197-206.
Ref 533416J Med Chem. 1988 Oct;31(10):1941-6.Synthesis and pharmacological characterization of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines as dopamine receptor ligands.
Ref 533481J Med Chem. 1986 Oct;29(10):1904-12.Synthesis and dopaminergic binding of 2-aryldopamine analogues: phenethylamines, 3-benzazepines, and 9-(aminomethyl)fluorenes.
Ref 533512J Med Chem. 1980 Jun;23(6):635-43.Neuroleptic activity in 5-aryltetrahydro-gamma-carbolines.
Ref 533515J Med Chem. 1982 Oct;25(10):1133-40.Effects of conformationally restricted 4-piperazinyl-10H-thienobenzodiazepine neuroleptics on central dopaminergic and cholinergic systems.
Ref 533570J Med Chem. 1982 Jul;25(7):855-8.Affinity of 10-(4-methylpiperazino)dibenz[b,f]oxepins for clozapine and spiroperidol binding sites in rat brain.
Ref 533577J Med Chem. 1981 Sep;24(9):1021-6.Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain.
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