Dopamine receptor D3

Dopamine receptor D3

Dopamine receptor D3

Dopamine D3 receptor with Eticlopride(PDB )
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; D3DR; ETM1; FET1
External IDs IUPHAR: ChEMBL: GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

D3 dopamine receptor is a protein that in humans is encoded by the DRD3 gene.[1][2]

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.[3] 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).[2]

D3 agonists like 7-OH-DPAT, pramipexole, and rotigotine, among others, display antidepressant effects in rodent models of depression.[4][5]


  • Ligands 1
    • Agonists 1.1
    • Partial agonists 1.2
    • Antagonists 1.3
  • Interactions 2
  • See also 3
  • References 4
  • Further reading 5
  • External links 6



Partial agonists



Dopamine receptor D3 has been shown to interact with CLIC6[21] and EPB41L1.[22]

See also


  1. ^ 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.  
  2. ^ a b "Entrez Gene: DRD3 dopamine receptor D3". 
  3. ^ 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.  
  4. ^ Breuer ME, Groenink L, Oosting RS, et al. (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.  
  5. ^ 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.  
  6. ^ 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.  
  7. ^ 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.  
  8. ^ 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.  
  9. ^ Peglion JL, Poitevin C, La Cour CM, 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.  
  10. ^ 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.  
  11. ^ Collins, G. T.; Butler, P.; Wayman, C.; Ratcliffe, S.; Gupta, P.; Oberhofer, G.; Caine, S. B. (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.  
  12. ^ 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.  
  13. ^ 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.  
  14. ^ Chen J, Collins GT, Zhang J, et al. (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.  
  15. ^ 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.  
  16. ^ a b 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.  
  17. ^ Grundt P, Carlson EE, Cao J, et al (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.  
  18. ^ Mason, C. W.; Hassan, H. E.; Kim, K. P.; Cao, J.; Eddington, N. D.; Newman, A. H.; Voulalas, P. J. (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.  
  19. ^ Newman AH, Grundt P, Cyriac G, et al. (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.  
  20. ^ 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.  
  21. ^ 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.  
  22. ^ 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.  

Further reading

  • Missale C, Nash SR, Robinson SW, et al. (1998). "Dopamine receptors: from structure to function.". Physiol. Rev. 78 (1): 189–225.  
  • Sidhu A, Niznik HB (2000). "Coupling of dopamine receptor subtypes to multiple and diverse G proteins.". Int. J. Dev. Neurosci. 18 (7): 669–77.  
  • Sokoloff P, Giros B, Martres MP, et al. (1990). "Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics.". Nature 347 (6289): 146–51.  
  • Giros B, Martres MP, Sokoloff P, Schwartz JC (1991). "[Gene cloning of human dopaminergic D3 receptor and identification of its chromosome]". C. R. Acad. Sci. III, Sci. Vie 311 (13): 501–8.  
  • Liu K, Bergson C, Levenson R, Schmauss C (1994). "On the origin of mRNA encoding the truncated dopamine D3-type receptor D3nf and detection of D3nf-like immunoreactivity in human brain.". J. Biol. Chem. 269 (46): 29220–6.  
  • Schmauss C, Haroutunian V, Davis KL, Davidson M (1993). "Selective loss of dopamine D3-type receptor mRNA expression in parietal and motor cortices of patients with chronic schizophrenia.". Proc. Natl. Acad. Sci. U.S.A. 90 (19): 8942–6.  
  • Griffon N, Crocq MA, Pilon C, et al. (1996). "Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia.". Am. J. Med. Genet. 67 (1): 63–70.  
  • Staley JK, Mash DC (1996). "Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities.". J. Neurosci. 16 (19): 6100–6.  
  • Chen CH, Liu MY, Wei FC, et al. (1997). "Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia.". Am. J. Med. Genet. 74 (1): 40–3.  
  • Gulcher JR, Jónsson P, Kong A, et al. (1997). "Mapping of a familial essential tremor gene, FET1, to chromosome 3q13.". Nat. Genet. 17 (1): 84–7.  
  • Oldenhof J, Vickery R, Anafi M, et al. (1998). "SH3 binding domains in the dopamine D4 receptor.". Biochemistry 37 (45): 15726–36.  
  • Cargill M, Altshuler D, Ireland J, et al. (1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes.". Nat. Genet. 22 (3): 231–8.  
  • Pilla M, Perachon S, Sautel F, et al. (1999). "Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist.". Nature 400 (6742): 371–5.  
  • Ilani T, Ben-Shachar D, Strous RD, et al. (2001). "A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes.". Proc. Natl. Acad. Sci. U.S.A. 98 (2): 625–8.  
  • Lin R, Karpa K, Kabbani N, et al. (2001). "Dopamine D2 and D3 receptors are linked to the actin cytoskeleton via interaction with filamin A.". Proc. Natl. Acad. Sci. U.S.A. 98 (9): 5258–63.  
  • Oldenhof J, Ray A, Vickery R, Van Tol HH (2001). "SH3 ligands in the dopamine D3 receptor.". Cell. Signal. 13 (6): 411–6.  
  • Soma M, Nakayama K, Rahmutula D, et al. (2002). "Ser9Gly polymorphism in the dopamine D3 receptor gene is not associated with essential hypertension in the Japanese.". Med. Sci. Monit. 8 (1): CR1–4.  

External links

  • "3"Dopamine Receptors: D. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 
  • Receptors, Dopamine D3 at the US National Library of Medicine Medical Subject Headings (MeSH)

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