Open Access Articles- Top Results for Dopamine receptor D1

Dopamine receptor D1

SymbolsDRD1 ; DADR; DRD1A
External IDsOMIM126449 MGI99578 HomoloGene30992 IUPHAR: 214 ChEMBL: 2056 GeneCards: DRD1 Gene
RNA expression pattern
File:PBB GE DRD1 214652 at tn.png
More reference expression data
RefSeq (mRNA)NM_000794NM_001291801
RefSeq (protein)NP_000785NP_001278730
Location (UCSC)Chr 5:
174.87 – 174.87 Mb
Chr 13:
54.05 – 54.06 Mb
PubMed search[1][2]

Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.[1][2][3]


This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G protein-coupled receptor stimulates adenylate cyclase and indirectly activates cyclic AMP-dependent protein kinases. D1 receptors regulate neuronal growth and development, mediate some behavioral responses, and modulate dopamine receptor D2-mediated events.[4] Alternate transcription initiation sites result in two transcript variants of this gene.[5]


The DRD1 gene expresses primarily in the caudate putamen in humans, and in the caudate putamen, the nucleus accumbens and the olfactory tubercle in mouse. Gene expression patterns from the Allen Brain Atlases in mouse and human can be found here.


There are a number of ligands selective for the D1 receptors. To date, most of the known ligands are based on dihydrexidine or the prototypical benzazepine partial agonist SKF-38393 (one derivative being the prototypical antagonist SCH-23390).[6] D1 receptor has a high degree of structural homologine to another dopamine receptor, D5, and they both bind similar drugs.[7] As a result, none of the known ligands is selective for the D1 vs. the D5 receptor, but the benzazepines generally are more selective for the D1 and D5 receptors versus the D2-like family.[6] Some of the benzazepines have high intrinsic activity whereas others do not.


File:D1 agonists.png
Chemical structures of selective D1 receptor agonists.[8][9]
  • Dihydrexidine derivatives
    • A-86929 - full agonist with 14-fold selectivity for D1-like receptors over D2[6][9][10]
    • Dihydrexidine - full agonist with 10-fold selectivity for D1-like receptors over D2 that has been in Phase IIa clinical trials as a cognitive enhancer.[11][12] It also showed profound antiparkinson effects in MPTP-treated primates,[13] but caused profound hypotension in one early clinical trial in Parkinson's disease.[6] Although dihydrexidine has significant D2 properties, it is highly biased at D2 receptors and was used for the first demonstration of functional selectivity[14] with dopamine receptors.[15][16]
    • Dinapsoline - full agonist with 5-fold selectivity for D1-like receptors over D2[6]
    • Dinoxyline - full agonist with approximately equal affinity for D1-like and D2 receptors[6]
    • Doxanthrine - full agonist with 168-fold selectivity for D1-like receptors over D2[6]
  • Benzazepine derivatives
  • Others
    • Stepholidine - alkaloid with D1 agonist and D2 antagonist properties, showing antipsychotic effects
    • A-68930
    • A-77636
    • CY-208,243 - high intrinsic activity partial agonist with moderate selectivity for D1-like over D2-like receptors, member of ergoline ligand family like pergolide and bromocriptine.
    • SKF-89145
    • SKF-89626
    • 7,8-Dihydroxy-5-phenyl-octahydrobenzo[h]isoquinoline: extremely potent, high-affinity full agonist[17]
    • Cabergoline - weak D1 agonism, highly selective for D2, and various serotonin receptors
    • Pergolide - (similar to cabergoline) weak D1 agonism, highly selective for D2, and various serotonin receptors


  • Benzazepine derivatives
    • SCH-23,390 - 100-fold selectivity for D1 over D5[6]
    • SKF-83,959 - 7-fold selectivity for D1 over D5 with negligible affinity for other receptors;[6] acts as an antagonist at D1 but as an agonist at D5
    • Ecopipam (SCH-39,166) - a selective D1/D5 antagonist that was being developed as an anti-obesity medication but was discontinued[6]

Protein-protein interactions

Dopamine receptor D1 has been shown to interact with:

Receptor oligomers

The D1 receptor forms heteromers with the following receptors: dopamine D2, D3,[20] histamine H3,[21] μ opioid.[22]

See also


  1. ^ Dearry A, Gingrich JA, Falardeau P, Fremeau RT, Bates MD, Caron MG (September 1990). "Molecular cloning and expression of the gene for a human D1 dopamine receptor". Nature 347 (6288): 72–6. PMID 2144334. doi:10.1038/347072a0. 
  2. ^ Zhou QY, Grandy DK, Thambi L, Kushner JA, Van Tol HH, Cone R et al. (September 1990). "Cloning and expression of human and rat D1dopamine receptors". Nature 347 (6288): 76–80. PMID 2168520. doi:10.1038/347076a0. 
  3. ^ Sunahara RK, Niznik HB, Weiner DM, Stormann TM, Brann MR, Kennedy JL et al. (September 1990). "Human dopamine D1 receptor encoded by an intronless gene on chromosome 5". Nature 347 (6288): 80–3. PMID 1975640. doi:10.1038/347080a0. 
  4. ^ 1992. "D1-like and D2-like dopamine receptors synergistically activate rotation and c-fos expression in the dopamine-depleted striatum in a rat model of Parkinson's disease". The Journal of Neuroscience 12 (10): 3729–3742. 
  5. ^ "Entrez Gene: DRD1 dopamine receptor D1". 
  6. ^ a b c d e f g h i j k l m n o Zhang J, Xiong B, Zhen X, Zhang A (2009). "Dopamine D1 receptor ligands: where are we now and where are we going.". Med Res Rev. 29 (2): 272–294. PMID 18642350. doi:10.1002/med.20130. 
  7. ^ Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G et al. (1991). "Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1". Nature 350 (6319): 614–9. PMID 1826762. doi:10.1038/350614a0. 
  8. ^ Cueva JP, Giorgioni G, Grubbs RA, Chemel BR, Watts VJ, Nichols DE (November 2006). "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". J. Med. Chem. 49 (23): 6848–57. PMID 17154515. doi:10.1021/jm0604979. 
  9. ^ a b Michaelides MR, Hong Y, DiDomenico S, Asin KE, Britton DR, Lin CW et al. (1995). "(5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1- ena[c]-phenanthrene-9,10-diol (A-86929): a potent and selective dopamine D1agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431)". J. Med. Chem. 38 (18): 3445–7. PMID 7658429. doi:10.1021/jm00018a002. 
  10. ^ Yamashita M, Yamada K, Tomioka K (2004). "Construction of arene-fused-piperidine motifs by asymmetric addition of 2-trityloxymethylaryllithiums to nitroalkenes: the asymmetric synthesis of a dopamine D1 full agonist, A-86929". J. Am. Chem. Soc. 126 (7): 1954–5. PMID 14971926. doi:10.1021/ja031760n. 
  11. ^ Mu Q, Johnson K, Morgan PS, Grenesko EL, Molnar CE, Anderson B et al. (2007). "A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia.". Schizophr Res. 94 (1-3): 332–341. PMID 17596915. doi:10.1016/j.schres.2007.03.033. 
  12. ^ George MS, Molnar CE, Grenesko EL, Anderson B, Mu Q, Johnson K et al. (2007). "A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia.". Schizophr Res. 93 (1-3): 42–50. PMID 17467956. doi:10.1016/j.schres.2007.03.011. 
  13. ^ Taylor JR, Lawrence MS, Redmond DE, Elsworth JD, Roth RH, Nichols DE et al. (1991). "Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys.". Eur J Pharmacol. 199 (3): 389–391. PMID 1680717. doi:10.1016/0014-2999(91)90508-N. 
  14. ^ Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H et al. (January 2007). "Functional selectivity and classical concepts of quantitative pharmacology". J. Pharmacol. Exp. Ther. 320 (1): 1–13. PMID 16803859. doi:10.1124/jpet.106.104463. 
  15. ^ Mottola DM, Kilts JD, Lewis MM, Connery HS, Walker QD, Jones SR et al. (June 2002). "Functional selectivity of dopamine receptor agonists. I. Selective activation of postsynaptic dopamine D2 receptors linked to adenylate cyclase". J. Pharmacol. Exp. Ther. 301 (3): 1166–78. PMID 12023552. doi:10.1124/jpet.301.3.1166. 
  16. ^ Kilts JD, Connery HS, Arrington EG, Lewis MM, Lawler CP, Oxford GS et al. (June 2002). "Functional selectivity of dopamine receptor agonists. II. Actions of dihydrexidine in D2L receptor-transfected MN9D cells and pituitary lactotrophs". J. Pharmacol. Exp. Ther. 301 (3): 1179–89. PMID 12023553. doi:10.1124/jpet.301.3.1179. 
  17. ^ Bonner LA, Chemel BR, Watts VJ, Nichols DE (September 2010). "Facile synthesis of octahydrobenzo[h]isoquinolines: novel and highly potent D1 dopamine agonists". Bioorg. Med. Chem. 18 (18): 6763–70. PMC 2941879. PMID 20709559. doi:10.1016/j.bmc.2010.07.052. 
  18. ^ a b Bermak JC, Li M, Bullock C, Weingarten P, Zhou QY (Feb 2002). "Interaction of gamma-COP with a transport motif in the D1 receptor C-terminus". Eur. J. Cell Biol. 81 (2): 77–85. PMID 11893085. doi:10.1078/0171-9335-00222. 
  19. ^ Bermak JC, Li M, Bullock C, Zhou QY (May 2001). "Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein". Nat. Cell Biol. 3 (5): 492–8. PMID 11331877. doi:10.1038/35074561. 
  20. ^ Marcellino D, Ferré S, Casadó V, Cortés A, Le Foll B, Mazzola C et al. (2008). "Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum". J. Biol. Chem. 283 (38): 26016–25. PMC 2533781. PMID 18644790. doi:10.1074/jbc.M710349200. 
  21. ^ Ferrada C, Moreno E, Casadó V, Bongers G, Cortés A, Mallol J et al. (2009). "Marked changes in signal transduction upon heteromerization of dopamine D1 and histamine H3 receptors". Br. J. Pharmacol. 157 (1): 64–75. PMC 2697789. PMID 19413572. doi:10.1111/j.1476-5381.2009.00152.x. 
  22. ^ Juhasz JR, Hasbi A, Rashid AJ, So CH, George SR, O'Dowd BF (2008). "Mu-opioid receptor heterooligomer formation with the dopamine D1 receptor as directly visualized in living cells". Eur. J. Pharmacol. 581 (3): 235–43. PMID 18237729. doi:10.1016/j.ejphar.2007.11.060. 

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.