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This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia.
Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing.
- C132T, G423A, T765C, C939T, C957T, and G1101A
- -141C insertion/deletion The polymorphisms has been investigated with respect to association with schizophrenia.
Most of the older antipsychotic drugs such as chlorpromazine and haloperidol are antagonists for the dopamine D2 receptor, but are, in general, very unselective, at best selective only for the "D2-like family" receptors and so binding to D2, D3 and D4, and often also to many other receptors such as those for serotonin and histamine, resulting in a range of side-effects and making them poor agents for scientific research. In similar manner, older dopamine agonists used for Parkinson's disease such as bromocriptine and cabergoline are poorly selective for one dopamine receptor over another, and, although most of these agents do act as D2 agonists, they affect other subtypes as well. Several selective D2 ligands are, however, now available, and this number is likely to increase as further research progresses.
- Aplindore - partial agonist
- Aripiprazole (Abilify in USA) - partial agonist
- GSK-789,472 - mixed D2 partial agonist / D3 antagonist, with good selectivity over other receptors 
- Talipexole - selective for D2 over other dopamine receptors, but also acts as α2-adrenoceptor agonist and 5HT3 antagonist.
- Piribedil - also D3 receptor agonist and α2-adrenergic antagonist
- LSD - in vitro, LSD was found to be a partial agonist and potentiates dopamine-mediated prolactin secretion in lactotrophs. LSD is also a 5HT2A agonist.
- Pramipexole - also D3, D4 receptor agonist
- Quinpirole - also D3 receptor agonist
- Methylphenidate[How to reference and link to summary or text]
- Salvinorin A - partial agonist. Also k-opioid agonist.
- L-741,626 (3-[4-(4-Chlorophenyl)-4-hydroxypiperidin-l-yl]methyl-1H-indole) - highly selective D2 antagonist
- Melperone - D2 antagonist but also 5HT2A antagonist
- Risperidone - D2 antagonist but also 5HT2A antagonist
- Ziprasidone - D2 antagonist but also 5HT2A antagonist
- Raclopride - Radiolabled C11raclopride is commonly employed in Positron emission tomography studies
- Quetiapine 
- Domperidone - D2 and D3 antagonist
- D2Sh selective (presynaptic autoreceptors)
- ↑ Gene Overview of All Published Schizophrenia-Association Studies for DRD2. Schizophrenia Research Forum. URL accessed on 2009-06-09.
- ↑ Entrez Gene: DRD2 dopamine receptor D2.
- ↑ Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, Gejman PV (February 2003). Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum. Mol. Genet. 12 (3): 205–16.
- ↑ Arinami T, Gao M, Hamaguchi H, Toru M (April 1997). A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Hum. Mol. Genet. 6 (4): 577–82.
- ↑ Glatt SJ, Faraone SV, Tsuang MT (July 2004). DRD2 -141C insertion/deletion polymorphism is not associated with schizophrenia: results of a meta-analysis. Am. J. Med. Genet. B Neuropsychiatr. Genet. 128B (1): 21–3.
- ↑ Lucht M, Rosskopf D (July 2008). Comment on "Genetically determined differences in learning from errors". Science 321 (5886): 200; author reply 200.
- ↑ Clinical Pharmacology for Abilify. RxList.com. URL accessed on 2010-01-21.
- ↑ Holmes IP, Blunt RJ, Lorthioir OE, Blowers SM, Gribble A, Payne AH, Stansfield IG, Wood M, Woollard PM, Reavill C, Howes CM, Micheli F, Di Fabio R, Donati D, Terreni S, Hamprecht D, Arista L, Worby A, Watson SP (March 2010). The identification of a selective dopamine D2 partial agonist, D3 antagonist displaying high levels of brain exposure. Bioorganic & Medicinal Chemistry Letters 20 (6): 2013–6.
- ↑ Giacomelli S, Palmery M, Romanelli L, Cheng CY, Silvestrini B (1998). Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro. Life Sci. 63 (3): 215–22.
- ↑ Wang GJ, Volkow ND, Thanos PK, Fowler JS (2004). Similarity between obesity and drug addiction as assessed by neurofunctional imaging: a concept review. J Addict Dis 23 (3): 39–53.
- ↑ http://ajp.psychiatryonline.org/cgi/content/abstract/156/6/876
- ↑ Kamiya T, Saitoh O, Yoshioka K, Nakata H (June 2003). Oligomerization of adenosine A2A and dopamine D2 receptors in living cells. Biochem. Biophys. Res. Commun. 306 (2): 544–9.
- ↑ 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. Mol. Pharmacol. 62 (3): 507–13.
- ↑ Smith FD, Oxford GS, Milgram SL (July 1999). Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein. J. Biol. Chem. 274 (28): 19894–900.
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- Leysen JE, Gommeren W, Mertens J, et al. (1995). Comparison of in vitro binding properties of a series of dopamine antagonists and agonists for cloned human dopamine D2S and D2L receptors and for D2 receptors in rat striatal and mesolimbic tissues, using [125I] 2'-iodospiperone. Psychopharmacology (Berl.) 110 (1–2): 27–36.
- Itokawa M, Arinami T, Futamura N, et al. (1994). A structural polymorphism of human dopamine D2 receptor, D2(Ser311-->Cys). Biochem. Biophys. Res. Commun. 196 (3): 1369–75.
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- Cravchik A, Sibley DR, Gejman PV (1996). Functional analysis of the human D2 dopamine receptor missense variants. J. Biol. Chem. 271 (42): 26013–7.
- Ho MK, Wong YH (1997). Functional role of amino-terminal serine16 and serine27 of G alphaZ in receptor and effector coupling. J. Neurochem. 68 (6): 2514–22.
- Centonze D, Gubellini P, "et al." (2004). Differential contribution of dopamine D2S and D2L receptors in the modulation of glutamate and GABA transmission in the striatum. Neuroscience 129 (1): 157–66.
- MeSH Receptors,+Dopamine+D2
- Pappas, Stephanie Study: Genes Influence Who Your Friends Are. Imaginova Corp.. LiveScience. URL accessed on 20 January 2011.
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