Dopamine receptor D3

Dopamine receptor D3
Dopamine receptor D3

Dopamine D3 receptor with Eticlopride(PDB 3PBL)
Identifiers
Symbols DRD3; D3DR; ETM1; FET1; MGC149204; MGC149205
External IDs OMIM: 126451 MGI: 94925 HomoloGene: 623 GeneCards: DRD3 Gene
RNA expression pattern
PBB GE DRD3 211625 s at tn.png
PBB GE DRD3 214559 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1814 13490
Ensembl ENSG00000151577 ENSMUSG00000022705
UniProt P35462 Q0VEC4
RefSeq (mRNA) NM_000796.3 NM_007877.1
RefSeq (protein) NP_000787.2 NP_031903.1
Location (UCSC) Chr 3:
113.85 – 113.92 Mb		 Chr 16:
43.76 – 43.82 Mb
PubMed search [1] [2]

D(3) 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]

Contents

Ligands

Numerous non-selective prescription drugs bind to the D3 receptor, notably including some of the newer dopamine agonists used for Parkinson's disease such as pramipexole and ropinirole, but these also bind to D2 and lack the strong receptor type and subtype selectivity that some of the following research compounds afford:

Agonists

  • 8-OH-PBZI (cis-8-Hydroxy-3-(n-propyl)-1,2,3a,4,5,9b-hexahydro-1H-benz[e]indole)
  • PF-219,061 ((R)-3-(4-Propylmorpholin-2-yl)phenol): >1000-fold functional (efficiacy) selectivity over D2[6]
  • compound R,R-16: 250x binding selectivity over D2[7]
  • trans-N-{4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]cyclohexyl}-3-methoxybenzamide, full agonist, > 200-fold binding selectivity over D4, D2, 5-HT1A, and α1-receptors[8]
  • (-)-7-{[2-(4-Phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol[9]
  • BP-897: partial agonist [10]
  • FAUC 73
  • FAUC 460: partial agonist, outstanding affinity and selectivity[11]
  • FAUC 346: partial agonist, subtype selective[12]
  • PD-128,907
  • compound 12: partial agonist, Ki = 0.41nM, 800x binding selectivity over D2[13]
  • piribedil[14]

Antagonists

  • [15]
  • FAUC 365, silent antagonist, subtype selective[12]
  • compound 29 [16]
  • Nafadotride
  • NGB-2904[17]
  • 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
  • Domperidone - D2 and D3 antagonist
Chemical structures of selective D3 receptor ligands.


Interactions

Dopamine receptor D3 has been shown to interact with CLIC6[18] and EPB41L1.[19]

See also

References

  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. PMID 1916765. 
  2. ^ a b "Entrez Gene: DRD3 dopamine receptor D3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1814. 
  3. ^ Joyce, JN; Millan, MJ (2007 Feb). "Dopamine D3 receptor agonists for protection and repair in Parkinson's disease.". Current opinion in pharmacology 7 (1): 100-5. PMID 17174156. 
  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. doi:10.1016/j.ejphar.2009.06.029. PMID 19549514. http://linkinghub.elsevier.com/retrieve/pii/S0014-2999(09)00552-4. 
  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. doi:10.1016/j.ejphar.2006.07.022. PMID 16959244. http://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)00757-6. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2662387. 
  14. ^ 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. 
  15. ^ 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. doi:10.1021/jm900095y. PMC 2760932. PMID 19331412. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2760932. 
  16. ^ 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. doi:10.1021/jm049465g. PMID 15689168. 
  17. ^ 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. 
  18. ^ Griffon, Nathalie; Jeanneteau Freddy, Prieur Fanny, Diaz Jorge, Sokoloff Pierre (Sep. 2003). "CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors". Brain Res. Mol. Brain Res. (Netherlands) 117 (1): 47–57. doi:10.1016/S0169-328X(03)00283-3. ISSN 0169-328X. PMID 14499480. 
  19. ^ Binda, Alicia V; Kabbani Nadine, Lin Ridwan, Levenson Robert (Sep. 2002). "D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N". Mol. Pharmacol. (United States) 62 (3): 507–13. doi:10.1124/mol.62.3.507. ISSN 0026-895X. PMID 12181426. 

Further reading

External links

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