Dopamine receptor D1

DRD1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases DRD1, dopamine receptor D1, DADR, DRD1A
External IDs MGI: 99578 HomoloGene: 30992 GeneCards: DRD1
Targeted by Drug
a-68930, apomorphine, cabergoline, dopamine, fenoldopam, pergolide, rotigotine, serotonin, bromocriptine, lisuride, SKF-38393, (+)-butaclamol, chlorpromazine, clozapine, ecopipam, (Z)-flupentixol, fluphenazine, haloperidol, ketanserin, mesoridazine, prochlorperazine, SCH-23390, spiperone, thioridazine[1]
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

1812

13488

Ensembl

ENSG00000184845

ENSMUSG00000021478

UniProt

P21728

Q61616

RefSeq (mRNA)

NM_000794

NM_001291801
NM_010076

RefSeq (protein)

NP_000785.1

NP_001278730.1
NP_034206.1

Location (UCSC) Chr 5: 175.44 – 175.44 Mb Chr 13: 54.05 – 54.06 Mb
PubMed search [2] [3]
Wikidata
View/Edit HumanView/Edit Mouse

Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.[4][5][6]

Function

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.[7] Alternative transcription initiation sites result in two transcript variants of this gene.[8]

Production

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.

Ligands

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).[9] D1 receptor has a high degree of structural homologine to another dopamine receptor, D5, and they both bind similar drugs.[10] 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.[9] Some of the benzazepines have high intrinsic activity whereas others do not.

Agonists

Chemical structures of selective D1 receptor agonists.[11][12]

Several D1 receptor agonists are used clinically. These include apomorphine, pergolide, rotigotine, and terguride. All of these drugs are preferentially D2-like receptor agonists. Fenoldopam is a selective D1 receptor partial agonist that does not cross the blood-brain-barrier and is used intravenously in the treatment of hypertension. Dihydrexidine and adrogolide (ABT-431) (a prodrug of A-86929 with improved bioavailability) are the only selective, centrally active D1-like receptor agonists that have been studied clinically in humans.[13] They produced dose-limiting profound hypotension and dyskinesias, respectively, and were not further developed for clinical use.[13][14][15]

List of D1 receptor agonists

Antagonists

Many typical and atypical antipsychotics are D1 receptor antagonists in addition to D2 receptor antagonists. No other D1 receptor antagonists have been approved for clinical use. Ecopipam is a selective D1-like receptor antagonist that has been studied clinically in humans in the treatment of a variety of conditions, including schizophrenia, cocaine abuse, obesity, pathological gambling, and Tourette's syndrome, with efficacy in some of these conditions seen. The drug produced mild-to-moderate, reversible depression and anxiety in clinical studies however and has yet to complete development for any indication.

List of D1 receptor antagonists

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,[26] histamine H3,[27] μ opioid.[28]

See also

References

  1. ↑ "Drugs that physically interact with D(1A) dopamine receptor view/edit references on wikidata".
  2. ↑ "Human PubMed Reference:".
  3. ↑ "Mouse PubMed Reference:".
  4. ↑ 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. doi:10.1038/347072a0. PMID 2144334.
  5. ↑ Zhou QY, Grandy DK, Thambi L, Kushner JA, Van Tol HH, Cone R, Pribnow D, Salon J, Bunzow JR, Civelli O (September 1990). "Cloning and expression of human and rat D1dopamine receptors". Nature. 347 (6288): 76–80. doi:10.1038/347076a0. PMID 2168520.
  6. ↑ Sunahara RK, Niznik HB, Weiner DM, Stormann TM, Brann MR, Kennedy JL, Gelernter JE, Rozmahel R, Yang YL, Israel Y (September 1990). "Human dopamine D1 receptor encoded by an intronless gene on chromosome 5". Nature. 347 (6288): 80–3. doi:10.1038/347080a0. PMID 1975640.
  7. ↑ ML Paul; AM Graybiel; JC David; HA Robertson (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.
  8. ↑ "Entrez Gene: DRD1 dopamine receptor D1".
  9. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 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. doi:10.1002/med.20130. PMID 18642350.
  10. ↑ Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB (1991). "Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1". Nature. 350 (6319): 614–9. doi:10.1038/350614a0. PMID 1826762.
  11. ↑ 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. doi:10.1021/jm0604979. PMID 17154515.
  12. 1 2 Michaelides MR, Hong Y, DiDomenico S, Asin KE, Britton DR, Lin CW, Williams M, Shiosaki K (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. doi:10.1021/jm00018a002. PMID 7658429.
  13. 1 2 Rosell, Daniel R; Zaluda, Lauren C; McClure, Margaret M; Perez-Rodriguez, M Mercedes; Strike, K Sloan; Barch, Deanna M; Harvey, Philip D; Girgis, Ragy R; Hazlett, Erin A; Mailman, Richard B; Abi-Dargham, Anissa; Lieberman, Jeffrey A; Siever, Larry J (2014). "Effects of the D1 Dopamine Receptor Agonist Dihydrexidine (DAR-0100A) on Working Memory in Schizotypal Personality Disorder". Neuropsychopharmacology. 40 (2): 446–453. doi:10.1038/npp.2014.192. ISSN 0893-133X.
  14. ↑ Blanchet PJ, Fang J, Gillespie M, Sabounjian L, Locke KW, Gammans R, Mouradian MM, Chase TN (1998). "Effects of the full dopamine D1 receptor agonist dihydrexidine in Parkinson's disease". Clin Neuropharmacol. 21 (6): 339–43. PMID 9844789.
  15. ↑ Giardina, William J.; Williams, Michael (2006). "Adrogolide HCl (ABT-431; DAS-431), a Prodrug of the Dopamine D1 Receptor Agonist, A-86929: Preclinical Pharmacology and Clinical Data". CNS Drug Reviews. 7 (3): 305–316. doi:10.1111/j.1527-3458.2001.tb00201.x. ISSN 1080-563X.
  16. ↑ 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. doi:10.1021/ja031760n. PMID 14971926.
  17. ↑ Mu Q, Johnson K, Morgan PS, Grenesko EL, Molnar CE, Anderson B, Nahas Z, Kozel FA, Kose S, Knable M, Fernandes P, Nichols DE, Mailman RB, George MS (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. doi:10.1016/j.schres.2007.03.033. PMID 17596915.
  18. ↑ George MS, Molnar CE, Grenesko EL, Anderson B, Mu Q, Johnson K, Nahas Z, Knable M, Fernandes P, Juncos J, Huang X, Nichols DE, Mailman RB (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. doi:10.1016/j.schres.2007.03.011. PMID 17467956.
  19. ↑ Taylor JR, Lawrence MS, Redmond DE, Elsworth JD, Roth RH, Nichols DE, Mailman RB (1991). "Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys.". Eur J Pharmacol. 199 (3): 389–391. doi:10.1016/0014-2999(91)90508-N. PMID 1680717.
  20. ↑ Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller KJ, Spedding M, Mailman RB (January 2007). "Functional selectivity and classical concepts of quantitative pharmacology". J. Pharmacol. Exp. Ther. 320 (1): 1–13. doi:10.1124/jpet.106.104463. PMID 16803859.
  21. ↑ Mottola DM, Kilts JD, Lewis MM, Connery HS, Walker QD, Jones SR, Booth RG, Hyslop DK, Piercey M, Wightman RM, Lawler CP, Nichols DE, Mailman RB (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. doi:10.1124/jpet.301.3.1166. PMID 12023552.
  22. ↑ Kilts JD, Connery HS, Arrington EG, Lewis MM, Lawler CP, Oxford GS, O'Malley KL, Todd RD, Blake BL, Nichols DE, Mailman RB (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. doi:10.1124/jpet.301.3.1179. PMID 12023553.
  23. ↑ 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. doi:10.1016/j.bmc.2010.07.052. PMC 2941879Freely accessible. PMID 20709559.
  24. 1 2 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. doi:10.1078/0171-9335-00222. PMID 11893085.
  25. ↑ 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. doi:10.1038/35074561. PMID 11331877.
  26. ↑ Marcellino D, Ferré S, Casadó V, Cortés A, Le Foll B, Mazzola C, Drago F, Saur O, Stark H, Soriano A, Barnes C, Goldberg SR, Lluis C, Fuxe K, Franco R (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. doi:10.1074/jbc.M710349200. PMC 2533781Freely accessible. PMID 18644790.
  27. ↑ Ferrada C, Moreno E, Casadó V, Bongers G, Cortés A, Mallol J, Canela EI, Leurs R, Ferré S, Lluís C, Franco R (2009). "Marked changes in signal transduction upon heteromerization of dopamine D1 and histamine H3 receptors". Br. J. Pharmacol. 157 (1): 64–75. doi:10.1111/j.1476-5381.2009.00152.x. PMC 2697789Freely accessible. PMID 19413572.
  28. ↑ 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. doi:10.1016/j.ejphar.2007.11.060. PMID 18237729.
  29. ↑ Rodríguez-Ruiz M, Moreno E, Moreno-Delgado D, Navarro G, Mallol J, Cortés A, Lluís C, Canela EI, Casadó V, McCormick PJ, Franco R (2016). "Heteroreceptor Complexes Formed by Dopamine D1, Histamine H3, and N-Methyl-D-Aspartate Glutamate Receptors as Targets to Prevent Neuronal Death in Alzheimer's Disease". Mol. Neurobiol. doi:10.1007/s12035-016-9995-y. PMID 27370794.

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