Dopamine receptor D3 is a protein that in humans is encoded by the DRD3gene.[5][6]
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.[citation needed] It is a target for drugs which treat schizophrenia, drug addiction, and Parkinson's disease.[7] 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).[6]
D3 agonists like 7-OH-DPAT, pramipexole, and rotigotine, among others, display antidepressant effects in rodent models of depression.[8][9]
Animal studies[]
D3 agonists have been shown to disrupt prepulse inhibition of startle (PPI), a cross-species measure that recapitulates deficits in sensorimotor gating in neuropsychiatric disorders such as schizophrenia.[10][11][12] In contrast, D3-preferring antagonists have antipsychotic-like profiles in measures of PPI in rats.[13]
Ligands[]
Agonists[]
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[14]
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
(highly selective)
Sulpiride (also D2 antagonist)
U99194
(high affinity and selectivity)
Risperidone
Interactions[]
Dopamine receptor D3 has been shown to interact with CLIC6[30] and EPB41L1.[31]
^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. PMID17174156.
^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. PMID19549514.
^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. PMID16959244.
^Leopoldo M, Lacivita E, Colabufo NA, Berardi F, Perrone R (February 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". The Journal of Pharmacy and Pharmacology. 58 (2): 209–18. doi:10.1211/jpp.58.2.0008. PMID16451749. S2CID42910160.
^Biswas S, Zhang S, Fernandez F, Ghosh B, Zhen J, Kuzhikandathil E, Reith ME, Dutta AK (January 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". Journal of Medicinal Chemistry. 51 (1): 101–17. doi:10.1021/jm070860r. PMID18072730.
^Perachon, Sylvie; Schwartz, Jean-Charles; Sokoloff, Pierre (February 1999). "Functional potencies of new antiparkinsonian drugs at recombinant human dopamine D1, D2 and D3 receptors". European Journal of Pharmacology. 366 (2–3): 293–300. doi:10.1016/S0014-2999(98)00896-6. PMID10082211.
^Peglion JL, Poitevin C, Mannoury La Cour C, Dupuis D, Millan MJ (April 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". Bioorganic & Medicinal Chemistry Letters. 19 (8): 2133–8. doi:10.1016/j.bmcl.2009.03.015. PMID19324548.
^Blagg J, Allerton CM, Batchelor DV, Baxter AD, Burring DJ, Carr CL, Cook AS, Nichols CL, Phipps J, Sanderson VG, Verrier H, Wong S (December 2007). "Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route". Bioorganic & Medicinal Chemistry Letters. 17 (24): 6691–6. doi:10.1016/j.bmcl.2007.10.059. PMID17976986.
^Cagnotto A, Parotti L, Mennini T (October 1996). "In vitro affinity of piribedil for dopamine D3 receptor subtypes, an autoradiographic study". European Journal of Pharmacology. 313 (1–2): 63–7. doi:10.1016/0014-2999(96)00503-1. PMID8905329.
^Dörfler M, Tschammer N, Hamperl K, Hübner H, Gmeiner P (November 2008). "Novel D3 selective dopaminergics incorporating enyne units as nonaromatic catechol bioisosteres: synthesis, bioactivity, and mutagenesis studies". Journal of Medicinal Chemistry. 51 (21): 6829–38. doi:10.1021/jm800895v. PMID18834111.
^ Jump up to: abBettinetti L, Schlotter K, Hübner H, Gmeiner P (October 2002). "Interactive SAR studies: rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists". Journal of Medicinal Chemistry. 45 (21): 4594–7. doi:10.1021/jm025558r. PMID12361386.
^Grundt P, Carlson EE, Cao J, Bennett CJ, McElveen E, Taylor M, Luedtke RR, Newman AH (February 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". Journal of Medicinal Chemistry. 48 (3): 839–48. doi:10.1021/jm049465g. PMID15689168.
^Griffon N, Jeanneteau F, Prieur F, Diaz J, Sokoloff P (September 2003). "CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors". Brain Research. Molecular Brain Research. 117 (1): 47–57. doi:10.1016/S0169-328X(03)00283-3. PMID14499480.
^Binda AV, Kabbani N, Lin R, Levenson R (September 2002). "D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N". Molecular Pharmacology. 62 (3): 507–13. doi:10.1124/mol.62.3.507. PMID12181426.
Further reading[]
Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (January 1998). "Dopamine receptors: from structure to function". Physiological Reviews. 78 (1): 189–225. doi:10.1152/physrev.1998.78.1.189. PMID9457173.
Sidhu A, Niznik HB (November 2000). "Coupling of dopamine receptor subtypes to multiple and diverse G proteins". International Journal of Developmental Neuroscience. 18 (7): 669–77. doi:10.1016/S0736-5748(00)00033-2. PMID10978845. S2CID21002590.
Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (September 1990). "Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics". Nature. 347 (6289): 146–51. doi:10.1038/347146a0. PMID1975644. S2CID4284114.
Giros B, Martres MP, Sokoloff P, Schwartz JC (1991). "[Gene cloning of human dopaminergic D3 receptor and identification of its chromosome]". Comptes Rendus de l'Académie des Sciences, Série III. 311 (13): 501–8. PMID2129115.
Griffon N, Crocq MA, Pilon C, Martres MP, Mayerova A, Uyanik G, Burgert E, Duval F, Macher JP, Javoy-Agid F, Tamminga CA, Schwartz JC, Sokoloff P (February 1996). "Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia". American Journal of Medical Genetics. 67 (1): 63–70. doi:10.1002/(SICI)1096-8628(19960216)67:1<63::AID-AJMG11>3.0.CO;2-N. PMID8678117.
Chen CH, Liu MY, Wei FC, Koong FJ, Hwu HG, Hsiao KJ (February 1997). "Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia". American Journal of Medical Genetics. 74 (1): 40–3. doi:10.1002/(SICI)1096-8628(19970221)74:1<40::AID-AJMG9>3.0.CO;2-Z. PMID9034004.
Gulcher JR, Jónsson P, Kong A, Kristjánsson K, Frigge ML, Kárason A, Einarsdóttir IE, Stefánsson H, Einarsdóttir AS, Sigurthoardóttir S, Baldursson S, Björnsdóttir S, Hrafnkelsdóttir SM, Jakobsson F, Benedickz J, Stefánsson K (September 1997). "Mapping of a familial essential tremor gene, FET1, to chromosome 3q13". Nature Genetics. 17 (1): 84–7. doi:10.1038/ng0997-84. PMID9288103. S2CID1506516.
Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES (July 1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nature Genetics. 22 (3): 231–8. doi:10.1038/10290. PMID10391209. S2CID195213008.
Pilla M, Perachon S, Sautel F, Garrido F, Mann A, Wermuth CG, Schwartz JC, Everitt BJ, Sokoloff P (July 1999). "Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist". Nature. 400 (6742): 371–5. doi:10.1038/22560. PMID10432116. S2CID4351316.
Oldenhof J, Ray A, Vickery R, Van Tol HH (June 2001). "SH3 ligands in the dopamine D3 receptor". Cellular Signalling. 13 (6): 411–6. doi:10.1016/S0898-6568(01)00157-7. PMID11384839.
Soma M, Nakayama K, Rahmutula D, Uwabo J, Sato M, Kunimoto M, Aoi N, Kosuge K, Kanmatsuse K (January 2002). "Ser9Gly polymorphism in the dopamine D3 receptor gene is not associated with essential hypertension in the Japanese". Medical Science Monitor. 8 (1): CR1-4. PMID11796958.
External links[]
"Dopamine Receptors: D3". 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.
