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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. The dopamine-D3 receptor is highly concentrated in the nucleus accumbens and is also influential in the medial prefrontal cortex.[3] Action at this receptor is correlated with reinforcement and reward systems through its influence on Protein kinase A (PKA) regulation of the GABA receptor GABAA.[3] It is a target for drugs which treat schizophrenia, drug addiction, and Parkinson's disease.[4] 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.[5][6]

Ligands

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Agonists

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Partial agonists

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Antagonists

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Interactions

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Dopamine receptor D3 has been shown to interact with CLIC6[22] and EPB41L1.[23]

See also

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References

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  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. doi:10.1007/bf00209024. PMID 1916765.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ a b "Entrez Gene: DRD3 dopamine receptor D3".
  3. ^ a b Chen, G; Kittler, JT; Moss, SJ; Yan, Z (1 March 2006). "Dopamine D3 receptors regulate GABAA receptor function through a phospho-dependent endocytosis mechanism in nucleus accumbens". The Journal of Neuroscience : The Official Journal of the Society for Neuroscience. 26 (9): 2513–21. doi:10.1523/JNEUROSCI.4712-05.2006. PMC 6793654. PMID 16510729.
  4. ^ 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.
  5. ^ 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. doi:10.1016/j.ejphar.2009.06.029. PMID 19549514. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  6. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ 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. PMC 3224040. PMID 22125662.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ 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. doi:10.1016/j.bmcl.2009.03.015. PMID 19324548.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ 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. doi:10.1097/FBP.0b013e3283536d21. PMC 3365486. PMID 22470105.
  13. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ 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. PMC 3713235. PMID 17985117.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ 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. doi:10.1021/jm800471h. PMC 2662387. PMID 18785726. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  16. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ 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. doi:10.1021/jm025558r. PMID 12361386.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ^ {{cite journal |author=Grundt P, Carlson EE, Cao J, et al |title=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 |journal=J. Med. Chem. |volume=48 |issue=3 |pages=839–48 |year=2005 |pmid=15689168 |doi=10.1021/jm049465g |url=}}
  19. ^ 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. doi:10.1124/jpet.109.165084. PMC 2879935. PMID 20228156.
  20. ^ 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. doi:10.1021/jm900095y. PMC 2760932. PMID 19331412. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  21. ^ 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. PMC 3771110. PMID 17627675.
  22. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  23. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Further reading

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

Category:G protein coupled receptors Category:Biology of attention deficit hyperactivity disorder

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