dopamine receptor D1

D₁ receptors are the most abundant kind of dopamine receptor in the central nervous system.{{cite journal | vauthors = Westerink RH | title = Targeting exocytosis: ins and outs of the modulation of quantal dopamine release | journal = CNS & Neurological Disorders Drug Targets | volume = 5 | issue = 1 | pages = 57–77 | date = February 2006 | pmid = 16613554 | doi = 10.2174/187152706784111597 | hdl-access = free | hdl = 1874/11642 }}

Northern blot and in situ hybridization show that the mRNA expression of DRD1 is highest in the dorsal striatum (caudate and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle).

Lower levels occur in the basolateral amygdala, cerebral cortex, septum, thalamus, and hypothalamus.{{cite book|vauthors=Schetz JA, Sibley DR| veditors = Sibley DR |title=Handbook of Contemporary Neuropharmacology|date=2007|publisher=Wiley-Interscience|location=Hoboken, NJ|isbn=9780471660538|page=226|chapter=Chapter 7: Dopaminergic Neurotransmission|quote=Localization of the D1 receptor messenger ribonucleic acid (mRNA) expression has been mapped using Northern analysis and in situ hybridization (for a review, see [54]). Expression of D1 receptor mRNA is highest in the caudate putamen, nucleus accumbens, and olfactory tubercle. Lower levels of expression are found in the basolateral amygdala, cerebral cortex, septum pellucidum, thalamus, and hypothalamus.}}

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.{{cite web |title=DRD1 search results |url=https://www.brain-map.org/search/index.html?query=drd1 |work = Allen Brain Atlas |publisher=Allen Institute for Brain Science |accessdate=2025-06-11}}

File:Dopamine d1 receptor in complex with agonist dopamine.png

The dopamine receptor D1 (D1R) is a Gs-coupled GPCR characterized by a canonical seven-transmembrane (TM) helical domain, with a ligand-binding pocket located extracellularly and a cytoplasmic G-protein interaction interface.{{cite journal | vauthors = Zhuang Y, Xu P, Mao C, Wang L, Krumm B, Zhou XE, Huang S, Liu H, Cheng X, Huang XP, Shen DD, Xu T, Liu YF, Wang Y, Guo J, Jiang Y, Jiang H, Melcher K, Roth BL, Zhang Y, Zhang C, Xu HE | title = Structural insights into the human D1 and D2 dopamine receptor signaling complexes | journal = Cell | volume = 184 | issue = 4 | pages = 931–942.e18 | date = February 2021 | pmid = 33571431 | pmc = 8215686 | doi = 10.1016/j.cell.2021.01.027 }}{{cite journal | vauthors = Sun B, Feng D, Chu ML, Fish I, Lovera S, Sands ZA, Kelm S, Valade A, Wood M, Ceska T, Kobilka TS, Lebon F, Kobilka BK | title = Crystal structure of dopamine D1 receptor in complex with G protein and a non-catechol agonist | journal = Nature Communications | volume = 12 | issue = 1 | pages = 3305 | date = June 2021 | pmid = 34083522 | pmc = 8175458 | doi = 10.1038/s41467-021-23519-9 | url = }} Cryo-EM and X-ray crystallography studies reveal that agonist binding induces conformational changes, including outward movement of TM6 and extension of TM5 by two helical turns, facilitating engagement with the Gαs subunit.{{cite journal | vauthors = Teng X, Chen S, Wang Q, Chen Z, Wang X, Huang N, Zheng S | title = Structural insights into G protein activation by D1 dopamine receptor | journal = Science Advances | volume = 8 | issue = 23 | pages = eabo4158 | date = June 2022 | pmid = 35687690 | pmc = 9187227 | doi = 10.1126/sciadv.abo4158 | url = }}

Agonist interact with extracellular loop 2 and extracellular regions of trans-membrane helices 2, 3, 6, and 7. Interactions between catechol-based agonists and three trans-membrane serine residues including S198^5.42, S199^5.43, and S202^5.46 function as microswitches that are essential for receptor activation.{{cite journal | vauthors = Zhuang Y, Krumm B, Zhang H, Zhou XE, Wang Y, Huang XP, Liu Y, Cheng X, Jiang Y, Jiang H, Zhang C, Yi W, Roth BL, Zhang Y, Xu HE | title = Mechanism of dopamine binding and allosteric modulation of the human D1 dopamine receptor | journal = Cell Research | volume = 31 | issue = 5 | pages = 593–596 | date = May 2021 | pmid = 33750903 | pmc = 8089099 | doi = 10.1038/s41422-021-00482-0 }}{{cite journal | vauthors = Sibley DR, Luderman KD, Free RB, Shi L | title = Novel Cryo-EM structures of the D1 dopamine receptor unlock its therapeutic potential | journal = Signal Transduction and Targeted Therapy | volume = 6 | issue = 1 | pages = 205 | date = May 2021 | pmid = 34023856 | pmc = 8141052 | doi = 10.1038/s41392-021-00630-3 }}

The ligand-binding pocket accommodates both catechol (e.g., dopamine, SKF81297) and non-catechol agonists, with selectivity influenced by residues like V317^7.39 and W321^7.43 in TM7, which form hydrophobic interactions rather than the polar contacts seen in β2-adrenergic receptors. Non-catechol agonists bind in an extended conformation, spanning the orthosteric site to extracellular loop 2 (ECL2), leveraging unique pocket topology for D1R specificity. Structural comparisons with D2R highlight divergent cytoplasmic features—D1R’s elongated TM5 and larger Gs interface (~1,520 Ų) contrast with D2R’s Gi-selective coupling, underpinning functional specificity. These insights provide templates for designing selective therapeutics targeting dopaminergic pathways.{{cite journal | vauthors = Sibley DR, Luderman KD, Free RB, Shi L | title = Novel Cryo-EM structures of the D1 dopamine receptor unlock its therapeutic potential | journal = Signal Transduction and Targeted Therapy | volume = 6 | issue = 1 | pages = 205 | date = May 2021 | pmid = 34023856 | pmc = 8141052 | doi = 10.1038/s41392-021-00630-3 }}

D₁ receptors regulate the memory, learning, and the growth of neurons, also is used in the reward system and locomotor activity, mediating some behaviors and modulating dopamine receptor D₂-mediated events.{{cite journal | vauthors = Paul ML, Graybiel AM, David JC, Robertson HA | title = 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 | journal = The Journal of Neuroscience | volume = 12 | issue = 10 | pages = 3729–3742 | date = October 1992 | pmid = 1357113 | pmc = 6575976 | doi = 10.1523/JNEUROSCI.12-10-03729.1992 }}

They play a role in addiction by facilitating the gene expression changes that occur in the nucleus accumbens during addiction.

They are Gs coupled and can stimulate neurons by activation of cyclic AMP-dependent protein kinase.

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).{{cite journal | vauthors = Zhang J, Xiong B, Zhen X, Zhang A | title = Dopamine D1 receptor ligands: where are we now and where are we going | journal = Medicinal Research Reviews | volume = 29 | issue = 2 | pages = 272–294 | date = March 2009 | pmid = 18642350 | doi = 10.1002/med.20130 | s2cid = 25334596 }} D₁ receptor has a high degree of structural homology to another dopamine receptor, D₅, and they both bind similar drugs.{{cite journal | vauthors = Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB | title = Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1 | journal = Nature | volume = 350 | issue = 6319 | pages = 614–619 | date = April 1991 | pmid = 1826762 | doi = 10.1038/350614a0 | s2cid = 4373022 | bibcode = 1991Natur.350..614S }} As a result, none of the known orthosteric 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. Some of the benzazepines have high intrinsic activity whereas others do not. In 2015 the first positive allosteric modulator for the human D₁ receptor was discovered by high-throughput screening.{{cite journal | vauthors = Lewis MA, Hunihan L, Watson J, Gentles RG, Hu S, Huang Y, Bronson J, Macor JE, Beno BR, Ferrante M, Hendricson A, Knox RJ, Molski TF, Kong Y, Cvijic ME, Rockwell KL, Weed MR, Cacace AM, Westphal RS, Alt A, Brown JM | title = Discovery of D1 Dopamine Receptor Positive Allosteric Modulators: Characterization of Pharmacology and Identification of Residues that Regulate Species Selectivity | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 354 | issue = 3 | pages = 340–349 | date = September 2015 | pmid = 26109678 | doi = 10.1124/jpet.115.224071 | doi-access = free }}

Image:D1 agonists.png

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.{{cite journal | vauthors = Rosell DR, Zaluda LC, McClure MM, Perez-Rodriguez MM, Strike KS, Barch DM, Harvey PD, Girgis RR, Hazlett EA, Mailman RB, Abi-Dargham A, Lieberman JA, Siever LJ | title = Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder | journal = Neuropsychopharmacology | volume = 40 | issue = 2 | pages = 446–453 | date = January 2015 | pmid = 25074637 | pmc = 4443959 | doi = 10.1038/npp.2014.192 }} The selective D₁ agonists give profound antiparkinson effects in humans and primate models of PD, and yield cognitive enhancement in many preclinical models and a few clinical trials. The most dose-limiting feature is profound hypotension, but the clinical development was impeded largely by lack of oral bioavailability and short duration of action.{{cite journal | vauthors = Blanchet PJ, Fang J, Gillespie M, Sabounjian L, Locke KW, Gammans R, Mouradian MM, Chase TN | title = Effects of the full dopamine D1 receptor agonist dihydrexidine in Parkinson's disease | journal = Clinical Neuropharmacology | volume = 21 | issue = 6 | pages = 339–343 | year = 1998 | pmid = 9844789 }}{{cite journal | vauthors = Giardina WJ, Williams M | title = Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D1 receptor agonist, A-86929: preclinical pharmacology and clinical data | journal = CNS Drug Reviews | volume = 7 | issue = 3 | pages = 305–316 | year = 2006 | pmid = 11607045 | pmc = 6741696 | doi = 10.1111/j.1527-3458.2001.tb00201.x }} In 2017, Pfizer made public information about pharmaceutically-acceptable non-catechol selective D₁ agonists that are in clinical development.

• Dihydrexidine derivatives
• A-86929{{snd}} full agonist with 14-fold selectivity for D₁-like receptors over D₂{{cite journal | vauthors = Michaelides MR, Hong Y, DiDomenico S, Asin KE, Britton DR, Lin CW, Williams M, Shiosaki K | title = (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 D1 agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431) | journal = Journal of Medicinal Chemistry | volume = 38 | issue = 18 | pages = 3445–3447 | date = September 1995 | pmid = 7658429 | doi = 10.1021/jm00018a002 }}{{cite journal | vauthors = Yamashita M, Yamada K, Tomioka K | title = 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 | journal = Journal of the American Chemical Society | volume = 126 | issue = 7 | pages = 1954–1955 | date = February 2004 | pmid = 14971926 | doi = 10.1021/ja031760n }}
• Dihydrexidine{{snd}} full agonist with 10-fold selectivity for D₁-like receptors over D₂ that has been in Phase IIa clinical trials as a cognitive enhancer.{{cite journal | vauthors = 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 | title = A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia | journal = Schizophrenia Research | volume = 94 | issue = 1–3 | pages = 332–341 | date = August 2007 | pmid = 17596915 | doi = 10.1016/j.schres.2007.03.033 | s2cid = 25497605 }}{{cite journal | vauthors = 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 | title = A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia | journal = Schizophrenia Research | volume = 93 | issue = 1–3 | pages = 42–50 | date = July 2007 | pmid = 17467956 | doi = 10.1016/j.schres.2007.03.011 | s2cid = 31375175 }} It also showed profound antiparkinson effects in MPTP-treated primates,{{cite journal | vauthors = Taylor JR, Lawrence MS, Redmond DE, Elsworth JD, Roth RH, Nichols DE, Mailman RB | title = Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys | journal = European Journal of Pharmacology | volume = 199 | issue = 3 | pages = 389–391 | date = July 1991 | pmid = 1680717 | doi = 10.1016/0014-2999(91)90508-N | doi-access = free }} but caused profound hypotension in one early clinical trial in Parkinson's disease. Although dihydrexidine has significant D₂ properties, it is highly biased at D₁ receptors and was used for the first demonstration of functional selectivity{{cite journal | vauthors = 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 | title = Functional selectivity and classical concepts of quantitative pharmacology | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 320 | issue = 1 | pages = 1–13 | date = January 2007 | pmid = 16803859 | doi = 10.1124/jpet.106.104463 | author8-link = Bryan Roth | s2cid = 447937 | url = https://cdr.lib.unc.edu/downloads/j9602272s }} with dopamine receptors.{{cite journal | vauthors = 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 | title = Functional selectivity of dopamine receptor agonists. I. Selective activation of postsynaptic dopamine D2 receptors linked to adenylate cyclase | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 301 | issue = 3 | pages = 1166–1178 | date = June 2002 | pmid = 12023552 | doi = 10.1124/jpet.301.3.1166 | s2cid = 2858428 }}{{cite journal | vauthors = Kilts JD, Connery HS, Arrington EG, Lewis MM, Lawler CP, Oxford GS, O'Malley KL, Todd RD, Blake BL, Nichols DE, Mailman RB | title = Functional selectivity of dopamine receptor agonists. II. Actions of dihydrexidine in D2L receptor-transfected MN9D cells and pituitary lactotrophs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 301 | issue = 3 | pages = 1179–1189 | date = June 2002 | pmid = 12023553 | doi = 10.1124/jpet.301.3.1179 }}
• Dinapsoline{{snd}} full agonist with 5-fold selectivity for D₁-like receptors over D₂
• Dinoxyline{{snd}} full agonist with approximately equal affinity for D₁-like and D₂ receptors
• Doxanthrine{{snd}} full agonist with 168-fold selectivity for D₁-like receptors over D₂
• Benzazepine derivatives
• SKF-81297{{snd}} 200-fold selectivity for D₁ over any other receptor
• SKF-82958{{snd}} 57-fold selectivity for D₁ over D₂
• SKF-38393{{snd}} very high selectivity for D₁ with negligible affinity for any other receptor
• Clozapine{{snd}} partial agonist at D₁-like receptors{{cite journal | vauthors = Ahlenius S | title = Clozapine: dopamine D1 receptor agonism in the prefrontal cortex as the code to decipher a Rosetta stone of antipsychotic drugs | journal = Pharmacology & Toxicology | volume = 84 | issue = 5 | pages = 193–196 | date = May 1999 | pmid = 10361974 | doi = 10.1111/j.1600-0773.1999.tb01482.x | doi-access = free }}
• Fenoldopam{{snd}} highly selective peripheral D₁ receptor partial agonist used clinically as an antihypertensive
• 6-Br-APB{{snd}} 90-fold selectivity for D₁ over D₂
• Trepipam (SCH-12679)
• Others
• Stepholidine{{snd}} alkaloid with D₁ agonist and D₂ antagonist properties, showing antipsychotic effects
• A-68930
• A-77636
• CY-208,243{{snd}} 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{{snd}} extremely potent, high-affinity full agonist{{cite journal | vauthors = Bonner LA, Chemel BR, Watts VJ, Nichols DE | title = Facile synthesis of octahydrobenzo[h]isoquinolines: novel and highly potent D1 dopamine agonists | journal = Bioorganic & Medicinal Chemistry | volume = 18 | issue = 18 | pages = 6763–6770 | date = September 2010 | pmid = 20709559 | pmc = 2941879 | doi = 10.1016/j.bmc.2010.07.052 }}
• Cabergoline{{snd}} weak D₁ agonism, highly selective for D₂, and various serotonin receptors
• Pergolide{{snd}} (similar to cabergoline) weak D₁ agonism, highly selective for D₂, and various serotonin receptors
• A photoswitchable agonist of D₁-like receptors (azodopa{{Cite journal | vauthors = Matera C, Calvé P, Casadó-Anguera V, Sortino R, Gomila AM, Moreno E, Gener T, Delgado-Sallent C, Nebot P, Costazza D, Conde-Berriozabal S | date = January 2022 |title=Reversible Photocontrol of Dopaminergic Transmission in Wild-Type Animals |journal=International Journal of Molecular Sciences |language=en |volume=23 |issue=17 |pages=10114 |doi=10.3390/ijms231710114 | pmid = 36077512 | pmc = 9456102 |issn=1422-0067 | doi-access = free }}) has been described that allows reversible control of dopaminergic transmission in wildtype animals.

• DETQ{{snd}} PAM{{cite journal | vauthors = Svensson KA, Heinz BA, Schaus JM, Beck JP, Hao J, Krushinski JH, Reinhard MR, Cohen MP, Hellman SL, Getman BG, Wang X, Menezes MM, Maren DL, Falcone JF, Anderson WH, Wright RA, Morin SM, Knopp KL, Adams BL, Rogovoy B, Okun I, Suter TM, Statnick MA, Gehlert DR, Nelson DL, Lucaites VL, Emkey R, DeLapp NW, Wiernicki TR, Cramer JW, Yang CR, Bruns RF | title = An Allosteric Potentiator of the Dopamine D1 Receptor Increases Locomotor Activity in Human D1 Knock-In Mice without Causing Stereotypy or Tachyphylaxis | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 360 | issue = 1 | pages = 117–128 | date = January 2017 | pmid = 27811173 | pmc = 5193077 | doi = 10.1124/jpet.116.236372 }}{{cite journal | vauthors = Bruns RF, Mitchell SN, Wafford KA, Harper AJ, Shanks EA, Carter G, O'Neill MJ, Murray TK, Eastwood BJ, Schaus JM, Beck JP, Hao J, Witkin JM, Li X, Chernet E, Katner JS, Wang H, Ryder JW, Masquelin ME, Thompson LK, Love PL, Maren DL, Falcone JF, Menezes MM, Zhang L, Yang CR, Svensson KA | title = Preclinical profile of a dopamine D1 potentiator suggests therapeutic utility in neurological and psychiatric disorders | journal = Neuropharmacology | volume = 128 | pages = 351–365 | date = January 2018 | pmid = 29102759 | doi = 10.1016/j.neuropharm.2017.10.032 | doi-access = free }}{{cite journal | vauthors = Wang X, Heinz BA, Qian YW, Carter JH, Gadski RA, Beavers LS, Little SP, Yang CR, Beck JP, Hao J, Schaus JM, Svensson KA, Bruns RF | title = Intracellular Binding Site for a Positive Allosteric Modulator of the Dopamine D1 Receptor | journal = Molecular Pharmacology | volume = 94 | issue = 4 | pages = 1232–1245 | date = October 2018 | pmid = 30111649 | doi = 10.1124/mol.118.112649 | doi-access = free }}
• Glovadalen (UCB-0022){{snd}} selective PAM, in phase 2 studies for Parkinson's disease
• Mevidalen (LY-3154207){{snd}} potent and subtype selective PAM, in phase 2 studies for Lewy body dementia.{{cite journal | vauthors = Hao J, Beck JP, Schaus JM, Krushinski JH, Chen Q, Beadle CD, Vidal P, Reinhard MR, Dressman BA, Massey SM, Boulet SL, Cohen MP, Watson BM, Tupper D, Gardinier KM, Myers J, Johansson AM, Richardson J, Richards DS, Hembre EJ, Remick DM, Coates DA, Bhardwaj RM, Diseroad BA, Bender D, Stephenson G, Wolfangel CD, Diaz N, Getman BG, Wang XS, Heinz BA, Cramer JW, Zhou X, Maren DL, Falcone JF, Wright RA, Mitchell SN, Carter G, Yang CR, Bruns RF, Svensson KA | title = Synthesis and Pharmacological Characterization of 2-(2,6-Dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a Potent, Subtype Selective, and Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor | journal = Journal of Medicinal Chemistry | volume = 62 | issue = 19 | pages = 8711–8732 | date = October 2019 | pmid = 31532644 | doi = 10.1021/acs.jmedchem.9b01234 | doi-access = free }}

Many typical and atypical antipsychotics are D₁ receptor antagonists in addition to D₂ receptor antagonists. But asenapine has shown stronger D₁ receptor affinity compared to other antipsychotics. 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.

• Berupipam (NNC 22-0010)
• Ecopipam (SCH-39,166){{snd}} a selective D₁/D₅ antagonist that was being developed as an anti-obesity medication but was discontinued However, it has showed promise in reducing stuttering and is currently in Phase 2 Trials for this purpose{{cite journal | vauthors = Maguire GA, LaSalle L, Hoffmeyer D, Nelson M, Lochhead JD, Davis K, Burris A, Yaruss JS | title = Ecopipam as a pharmacologic treatment of stuttering | journal = Annals of Clinical Psychiatry | volume = 31 | issue = 3 | pages = 164–168 | date = August 2019 | pmid = 31369655 | url = https://pubmed.ncbi.nlm.nih.gov/31369655/ }}{{cite web | url=https://emalexbiosciences.com/news/first-patient-dosed-in-emalex-biosciences-phase-2-clinical-trial-for-stuttering/ | title=First Patient Dosed in Emalex Biosciences Phase 2 Clinical Trial for Stuttering - Emalex Biosciences | date=15 December 2020 }}
• NNC 01-0687 (ADX-10061)
• Odapipam (NNC 01-0756)
• SCH-23,390{{snd}} 100-fold selectivity for D₁ over D₅

Dopamine receptor D₁ has been shown to interact with:

• COPG2
• COPG{{cite journal | vauthors = Bermak JC, Li M, Bullock C, Weingarten P, Zhou QY | title = Interaction of gamma-COP with a transport motif in the D1 receptor C-terminus | journal = European Journal of Cell Biology | volume = 81 | issue = 2 | pages = 77–85 | date = February 2002 | pmid = 11893085 | doi = 10.1078/0171-9335-00222 }}
• DNAJC14{{cite journal | vauthors = Bermak JC, Li M, Bullock C, Zhou QY | title = Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein | journal = Nature Cell Biology | volume = 3 | issue = 5 | pages = 492–498 | date = May 2001 | pmid = 11331877 | doi = 10.1038/35074561 | s2cid = 40809366 }}

The D₁ receptor forms heteromers with the following receptors: dopamine D₂ receptor, dopamine D₃ receptor,{{cite journal | vauthors = 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 | title = Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum | journal = The Journal of Biological Chemistry | volume = 283 | issue = 38 | pages = 26016–26025 | date = September 2008 | pmid = 18644790 | pmc = 2533781 | doi = 10.1074/jbc.M710349200 | doi-access = free }} histamine H₃ receptor,{{cite journal | vauthors = Ferrada C, Moreno E, Casadó V, Bongers G, Cortés A, Mallol J, Canela EI, Leurs R, Ferré S, Lluís C, Franco R | title = Marked changes in signal transduction upon heteromerization of dopamine D1 and histamine H3 receptors | journal = British Journal of Pharmacology | volume = 157 | issue = 1 | pages = 64–75 | date = May 2009 | pmid = 19413572 | pmc = 2697789 | doi = 10.1111/j.1476-5381.2009.00152.x }} μ opioid receptor,{{cite journal | vauthors = Juhasz JR, Hasbi A, Rashid AJ, So CH, George SR, O'Dowd BF | title = Mu-opioid receptor heterooligomer formation with the dopamine D1 receptor as directly visualized in living cells | journal = European Journal of Pharmacology | volume = 581 | issue = 3 | pages = 235–243 | date = March 2008 | pmid = 18237729 | doi = 10.1016/j.ejphar.2007.11.060 }} NMDA receptor, and adenosine A₁ receptor.{{cite journal | vauthors = Nishi A, Kuroiwa M, Shuto T | title = Mechanisms for the modulation of dopamine d(1) receptor signaling in striatal neurons | journal = Frontiers in Neuroanatomy | volume = 5 | pages = 43 | date = July 2011 | pmid = 21811441 | pmc = 3140648 | doi = 10.3389/fnana.2011.00043 | doi-access = free }}
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140648/figure/F2/ Dopamine D₁ receptor hetero-oligomers]

• D₁–D₂ receptor complex
• D₁−H₃−NMDAR receptor complex{{snd}} a target to prevent neurodegeneration{{cite journal | vauthors = Rodríguez-Ruiz M, Moreno E, Moreno-Delgado D, Navarro G, Mallol J, Cortés A, Lluís C, Canela EI, Casadó V, McCormick PJ, Franco R | title = 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 | journal = Molecular Neurobiology | volume = 54 | issue = 6 | pages = 4537–4550 | date = August 2017 | pmid = 27370794 | doi = 10.1007/s12035-016-9995-y | s2cid = 11203108 | url = https://ueaeprints.uea.ac.uk/id/eprint/59599/1/Rodriguez_et_ale.Proofing.pdf }}
• D₁–D3 receptor complex
• D₁–NMDAR receptor complex
• D₁–A₁ receptor complex

• Dopamine receptor

{{Reflist|2}}

• {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2252 | title = Dopamine Receptors: D₁ | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | access-date = 2008-12-04 | archive-date = 2015-01-02 | archive-url = https://web.archive.org/web/20150102110036/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2252 | url-status = dead }}
• {{MeshName|Receptors,+Dopamine+D1}}

{{NLM content}}

{{G protein-coupled receptors|g1}}

{{Dopaminergics}}

Category:Dopamine receptors