Dopamine receptor D3

Available structures
PDBOrtholog search: PDBe RCSB
Aliases DRD3, D3DR, ETM1, FET1, dopamine receptor D3
External IDs MGI: 94925 HomoloGene: 623 GeneCards: DRD3
Targeted by Drug
PF-592379, ropinirole, rotigotine, vilazodone, 7-hydroxy-2-(di-N-propylamino)tetralin, dopamine, pramipexole, quinelorane, quinpirole, apomorphine, do-687, bromocriptine, cabergoline, lisuride, pergolide, piribedil, roxindole, terguride, (+)-butaclamol, chlorpromazine, clozapine, domperidone, eticlopride, (Z)-flupentixol, haloperidol, loxapine, mesoridazine, nafadotride, nemonapride, perospirone, pimozide, prochlorperazine, promazine, raclopride, risperidone, SB-277,011-A, sertindole, spiperone, sulpiride, levosulpiride, zotepine[1]
RNA expression pattern

More reference expression data
Species Human Mouse









RefSeq (mRNA)


RefSeq (protein)



Location (UCSC) Chr 3: 114.13 – 114.2 Mb Chr 16: 43.76 – 43.82 Mb
PubMed search [2] [3]
View/Edit HumanView/Edit Mouse

Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.[4][5]

This gene encodes the D3 subtype of the dopamine receptor. The D3 subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that this receptor plays a role in cognitive and emotional functions. It is a target for drugs which treat schizophrenia, drug addiction, and Parkinson's disease.[6] Alternative splicing of this gene results in multiple transcript variants that would encode different isoforms, although some variants may be subject to nonsense-mediated decay (NMD).[5]

D3 agonists like 7-OH-DPAT, pramipexole, and rotigotine, among others, display antidepressant effects in rodent models of depression.[7][8]



Partial agonists


  • Most Antipsychotics
  • Amisulpride (non-selective)
  • Cyproheptadine (non-selective)
  • PG 01037 [20][21]
  • Domperidone (peripheral D2 and D3 antagonist)
  • FAUC 365, silent antagonist, subtype selective[19]
  • GR-103,691
  • GSK598809 (highly selective)
  • Haloperidol (non-selective, blocks all dopamine receptor subtypes)
  • N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides[22]
  • Nafadotride
  • NGB-2904[23]
  • PNU-99,194 (moderately selective over D2)
  • Raclopride (also D2 antagonist)
  • S-14,297 (selective)
  • S33084
  • SB-277011-A, selective D3 antagonist, 80x selectivity over D2 with no partial agonist effects, used in drug addiction research as a potential therapy for addiction to several different drugs
  • SR 21502 (highly selective)
  • Sulpiride (also D2 antagonist)
  • U99194
  • YQA14 (high affinity and selectivity)
  • Risperidone


Dopamine receptor D3 has been shown to interact with CLIC6[24] and EPB41L1.[25]

See also


  1. "Drugs that physically interact with D(3) dopamine receptor view/edit references on wikidata".
  2. "Human PubMed Reference:".
  3. "Mouse PubMed Reference:".
  4. Le Coniat M, Sokoloff P, Hillion J, Martres MP, Giros B, Pilon C, Schwartz JC, Berger R (Oct 1991). "Chromosomal localization of the human D3 dopamine receptor gene". Hum Genet. 87 (5): 618–20. doi:10.1007/bf00209024. PMID 1916765.
  5. 1 2 "Entrez Gene: DRD3 dopamine receptor D3".
  6. Joyce JN, Millan MJ (February 2007). "Dopamine D3 receptor agonists for protection and repair in Parkinson's disease.". Current Opinion in Pharmacology. 7 (1): 100–5. doi:10.1016/j.coph.2006.11.004. PMID 17174156.
  7. Breuer ME, Groenink L, Oosting RS, Buerger E, Korte M, Ferger B, Olivier B (August 2009). "Antidepressant effects of pramipexole, a dopamine D3/D2 receptor agonist, and 7-OH-DPAT, a dopamine D3 receptor agonist, in olfactory bulbectomized rats". European Journal of Pharmacology. 616 (1-3): 134–40. doi:10.1016/j.ejphar.2009.06.029. PMID 19549514.
  8. Bertaina-Anglade V, La Rochelle CD, Scheller DK (October 2006). "Antidepressant properties of rotigotine in experimental models of depression". European Journal of Pharmacology. 548 (1-3): 106–14. doi:10.1016/j.ejphar.2006.07.022. PMID 16959244.
  9. Leopoldo M, Lacivita E, Colabufo NA, Berardi F, Perrone R (2006). "Synthesis and binding profile of constrained analogues of N-[4-(4-arylpiperazin-1-yl)butyl]-3-methoxybenzamides, a class of potent dopamine D3 receptor ligands". J. Pharm. Pharmacol. 58 (2): 209–18. doi:10.1211/jpp.58.2.0008. PMID 16451749.
  10. Biswas S, Zhang S, Fernandez F, Ghosh B, Zhen J, Kuzhikandathil E, Reith ME, Dutta AK (2008). "Further structure-activity relationships study of hybrid 7-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol analogues: identification of a high-affinity D3-preferring agonist with potent in vivo activity with long duration of action". J. Med. Chem. 51 (1): 101–17. doi:10.1021/jm070860r. PMID 18072730.
  11. Chen J, Collins GT, Levant B, Woods J, Deschamps JR, Wang S (August 2011). "CJ-1639: A Potent and Highly Selective Dopamine D3 Receptor Full Agonist". ACS Med Chem Lett. 2 (8): 620–625. doi:10.1021/ml200100t. PMID 22125662.
  12. Peglion JL, Poitevin C, Mannoury La Cour C, Dupuis D, Millan MJ (2009). "Modulations of the amide function of the preferential dopamine D3 agonist (R,R)-S32504: Improvements of affinity and selectivity for D3 versus D2 receptors". Bioorg. Med. Chem. Lett. 19 (8): 2133–8. doi:10.1016/j.bmcl.2009.03.015. PMID 19324548.
  13. Blagg J, Allerton CM, Batchelor DV, Baxter AD, Burring DJ, Carr CL, Cook AS, Nichols CL, Phipps J, Sanderson VG, Verrier H, Wong S (2007). "Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route". Bioorg. Med. Chem. Lett. 17 (24): 6691–6. doi:10.1016/j.bmcl.2007.10.059. PMID 17976986.
  14. Collins GT, Butler P, Wayman C, Ratcliffe S, Gupta P, Oberhofer G, Caine SB (2012). "Lack of abuse potential in a highly selective dopamine D3 agonist, PF-592,379, in drug self-administration and drug discrimination in rats". Behavioural Pharmacology. 23 (3): 280–291. doi:10.1097/FBP.0b013e3283536d21. PMC 3365486Freely accessible. PMID 22470105.
  15. Cagnotto A, Parotti L, Mennini T (October 1996). "In vitro affinity of piribedil for dopamine D3 receptor subtypes, an autoradiographic study". Eur. J. Pharmacol. 313 (1-2): 63–7. doi:10.1016/0014-2999(96)00503-1. PMID 8905329.
  16. Spiller K, Xi ZX, Peng XQ, Newman AH, Ashby CR, Heidbreder C, Gaál J, Gardner EL (March 2008). "The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats". Psychopharmacology. 196 (4): 533–42. doi:10.1007/s00213-007-0986-6. PMID 17985117.
  17. Chen J, Collins GT, Zhang J, Yang CY, Levant B, Woods J, Wang S (2008). "Design, synthesis, and evaluation of potent and selective ligands for the dopamine 3 (D3) receptor with a novel in vivo behavioral profile". J. Med. Chem. 51 (19): 5905–8. doi:10.1021/jm800471h. PMC 2662387Freely accessible. PMID 18785726.
  18. Dörfler M, Tschammer N, Hamperl K, Hübner H, Gmeiner P (2008). "Novel D3 selective dopaminergics incorporating enyne units as nonaromatic catechol bioisosteres: synthesis, bioactivity, and mutagenesis studies". J. Med. Chem. 51 (21): 6829–38. doi:10.1021/jm800895v. PMID 18834111.
  19. 1 2 Bettinetti L, Schlotter K, Hübner H, Gmeiner P (2002). "Interactive SAR studies: rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists". J. Med. Chem. 45 (21): 4594–7. doi:10.1021/jm025558r. PMID 12361386.
  20. Grundt P, Carlson EE, Cao J, Bennett CJ, McElveen E, Taylor M, Luedtke RR, Newman AH (2005). "Novel heterocyclic trans olefin analogues of N-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl}arylcarboxamides as selective probes with high affinity for the dopamine D3 receptor". J. Med. Chem. 48 (3): 839–48. doi:10.1021/jm049465g. PMID 15689168.
  21. Mason CW, Hassan HE, Kim KP, Cao J, Eddington ND, Newman AH, Voulalas PJ (12 March 2010). "Characterization of the Transport, Metabolism, and Pharmacokinetics of the Dopamine D3 Receptor-Selective Fluorenyl- and 2-Pyridylphenyl Amides Developed for Treatment of Psychostimulant Abuse". Journal of Pharmacology and Experimental Therapeutics. 333 (3): 854–864. doi:10.1124/jpet.109.165084. PMID 20228156.
  22. Newman AH, Grundt P, Cyriac G, Deschamps JR, Taylor M, Kumar R, Ho D, Luedtke RR (2009). "N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonists ( parallel) ( perpendicular)". J. Med. Chem. 52 (8): 2559–70. doi:10.1021/jm900095y. PMC 2760932Freely accessible. PMID 19331412.
  23. Xi ZX, Gardner EL (2007). "Pharmacological actions of NGB 2904, a selective dopamine D3 receptor antagonist, in animal models of drug addiction". CNS Drug Reviews. 13 (2): 240–59. doi:10.1111/j.1527-3458.2007.00013.x. PMID 17627675.
  24. Griffon N, Jeanneteau F, Prieur F, Diaz J, Sokoloff P (2003). "CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors". Brain Res. Mol. Brain Res. 117 (1): 47–57. doi:10.1016/S0169-328X(03)00283-3. PMID 14499480.
  25. Binda AV, Kabbani N, Lin R, Levenson R (2002). "D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N". Mol. Pharmacol. 62 (3): 507–13. doi:10.1124/mol.62.3.507. PMID 12181426.

Further reading

External links

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