D4 receptor

Nomenclature: D4 receptor

Family: Dopamine receptors

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Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 467 11p15.5 DRD4 dopamine receptor D4 52
Mouse 7 387 7 F5 Drd4 dopamine receptor D4 28
Rat 7 387 1q41 Drd4 dopamine receptor D4 10
Previous and Unofficial Names
D4RA
D(4) dopamine receptor
Dopamine receptor D4
d(2C) dopamine receptor
dopamine D4 receptor
dopamine receptor 4
Drd-4
D4R
AW125663
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
dopamine
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
CP-226269 Rn Partial agonist 9.4 pKi 16
pKi 9.4 [16]
FAUC213 Rn Partial agonist 9.0 pKi 16
pKi 9.0 [16]
PD168,077 Rn Partial agonist 8.8 pKi 16
pKi 8.8 [16]
apomorphine Hs Partial agonist 8.4 pKi 24
pKi 8.4 [24]
lisuride Hs Partial agonist 8.3 pKi 24
pKi 8.3 [24]
roxindole Hs Partial agonist 8.2 pKi 24
pKi 8.2 [24]
A412997 Rn Agonist 8.1 pKi 25
pKi 8.1 (Ki 7.9x10-9 M) [25]
dopamine Hs Full agonist 7.6 pKi 52
pKi 7.6 [52]
quinpirole Hs Full agonist 7.5 pKi 24,30,52
pKi 7.5 [24,30,52]
dopamine Rn Full agonist 7.4 pKi 38
pKi 7.4 [38]
cabergoline Hs Partial agonist 7.3 pKi 24
pKi 7.3 [24]
rotigotine Hs Agonist 7.26 pKi 54
pKi 7.26 (Ki 5.5x10-8 M) [54]
pergolide Hs Partial agonist 7.2 pKi 24
pKi 7.2 [24]
fenoldopam Hs Full agonist 6.5 pKi 52
pKi 6.5 [52]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
nemonapride Hs Antagonist 10.0 pKd 41
pKd 10.0 [41]
[125I]L750667 Hs Antagonist 9.8 pKd 30
pKd 9.8 (Kd 1.6x10-10 M) [30]
[3H]spiperone Hs Antagonist 9.5 pKd 15,52
pKd 9.5 (Kd 3x10-10 M) [15,52]
[3H]NGD941 Hs Antagonist 8.3 pKd 33
pKd 8.3 (Kd 5x10-9 M) [33]
L-750,667 Rn Antagonist 10.0 pKi 38
pKi 10.0 [38]
RBI257 Rn Antagonist 9.6 pKi 16
pKi 9.6 [16]
NGD 94-1 Rn Antagonist 9.5 pKi 16
pKi 9.5 [16]
CP-293019 Rn Antagonist 9.5 pKi 16
pKi 9.5 [16]
[3H]N-methylspiperone Rn Antagonist 9.5 pKi 38
pKi 9.5 [38]
L745870 Hs Antagonist 9.4 pKi 17
pKi 9.4 [17]
spiperone Hs Antagonist 9.3 pKi 7
pKi 9.3 [7]
FAUC213 Rn Antagonist 9.0 pKi 16
pKi 9.0 [16]
sonepiprazole Hs Antagonist 8.9 pKi 39
pKi 8.9 (Ki 1.4x10-9 M) [39]
haloperidol Hs Antagonist 8.7 pKi 18,51
pKi 8.7 [18,51]
sonepiprazole Rn Antagonist 8.7 pKi 16
pKi 8.7 [16]
L741742 Hs Antagonist 8.5 pKi 36
pKi 8.5 [36]
terguride Hs Antagonist 8.1 pKi 24
pKi 8.1 [24]
Ro 10-4548 Rn Antagonist 7.8 pKi 16
pKi 7.8 [16]
chlorpromazine Hs Antagonist 7.8 pKi 18
pKi 7.8 [18]
clozapine Hs Antagonist 7.5 pKi 18
pKi 7.5 [18]
zotepine Hs Antagonist 7.41 pKi 40
pKi 7.41 (Ki 3.9x10-8 M) [40]
aripiprazole Rn Antagonist 7.3 pKi 38
pKi 7.3 [38]
eticlopride Hs Antagonist 7.0 pKi 7
pKi 7.0 [7]
(-)-sulpiride Hs Antagonist 5.72 – 7.7 pKi 30,50
pKi 5.72 – 7.7 (Ki 1.9x10-6 – 2x10-8 M) [30,50]
piribedil Hs Antagonist 6.5 pKi 24
pKi 6.5 [24]
bromocriptine Hs Antagonist 6.4 pKi 24
pKi 6.4 [24]
nafadotride Rn Antagonist 6.4 pKi 38
pKi 6.4 [38]
(+)-butaclamol Hs Antagonist 6.3 pKi 30
pKi 6.3 [30]
prochlorperazine Hs Antagonist 6.09 pKi 2
pKi 6.09 (Ki 8.1x10-7 M) [2]
raclopride Rn Antagonist 5.7 pKi 38
pKi 5.7 [38]
(+)-sulpiride Hs Antagonist 5.66 pKi 30
pKi 5.66 (Ki 2.2x10-6 M) [30]
View species-specific antagonist tables
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  31
Tissue Distribution
Brain: Occipital lobe, cerebellum, hippocampus, middle frontal gyrus of temporal lobe, middle frontal gyrus of frontal lobe, cingulate gyrus of frontal lobe, amygdala > superior temporal gyrus of temporal lobe, superior frontal gyrus of frontal lobe, thalamus, septal nuclei, hypothalamus > substantia nigra, caudate nucleus, globus pallidus, superior parietal lobe.
Species:  Human
Technique:  RT-PCR
References:  26
Brain: Pre-frontal cortex, temporal neocortex > occipital cortex.
Species:  Human
Technique:  in situ hybridization.
References:  22
Aortic endothelium, umbilical vein endothelium.
Species:  Human
Technique:  RT-PCR
References:  55
Pulmonary artery.
Species:  Human
Technique:  Western Blot and Immunohistochemistry.
References:  34
Brain (especially cerebellum), eye, adrenal gland, testes, superior cervical ganglion, submaxillary gland, pancreas.
Species:  Mouse
Technique:  RT-PCR
References:  47
Retina, photoreceptor cell layer and inner nuclear and ganglion cell layers.
Species:  Mouse
Technique:  RT-PCR and in situ hybridization.
References:  5
Striatum, substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus.
Species:  Rat
Technique:  Immunohistochemistry.
References:  35
Kidney: Cortical collecting duct.
Species:  Rat
Technique:  RT-PCR
References:  45
Kidney: Cortex > inner medulla.
Species:  Rat
Technique:  Western Blot and Immunocytochemistry.
References:  43
Nucleus accumbens shell.
Species:  Rat
Technique:  immunocytochemistry.
References:  48
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of cAMP levels in HEK 293 cells transfected with the human D4 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  3,11,21
Measurement of cAMP levels in CHO cells transfected with the human D4 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  1,4,19,29,42,49
Measurement of cAMP levels in COS-7 cells transfected with the human D4 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  1
Measurement of cAMP levels in Chinese hamster lung fibroblast CCL39 cells transfected with the rat D4 receptor.
Species:  Rat
Tissue:  Chinese hamster lung fibroblast CCL39 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  13
Measurement of high-voltage Ca2+ current in cultured granule cells from neonatal rat cerebellum endogenously expressing the D4 receptor.
Species:  Rat
Tissue:  Granule cells.
Response measured:  Inhibition of L-type Ca2+ current.
References:  23
Measurement of mitogenesis in CHO cells transfected with the human D4 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Mitogenesis.
References:  39
Measurement of Cl- currents in Xenopus oocytes transfected with murine D2L and D2S receptors.
Species:  Mouse
Tissue:  Xenopus oocytes.
Response measured:  Stimulation of Cl- influx.
References:  44
Measurement of inwardly rectifying K+ currents in Xenopus oocytes transfected with the human D4 receptor.
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  Activation of GIRK1 channels.
References:  32
Physiological Functions
Modulation of gastric acid secretion.
Species:  Rat
Tissue:  In vivo.
References:  14
Modulation of the dark level of light-sensitive cAMP in photoreceptors.
Species:  Mouse
Tissue:  Retina.
References:  5
Regulation of electrolyte and water transport.
Species:  Rat
Tissue:  Kidney.
References:  43,45
Modulation of von Willebrand factor secretion in endothelial cells.
Species:  Human
Tissue:  Endothelium.
References:  55
Physiological Consequences of Altering Gene Expression
D4 receptor knockout mice exhibit an increased sensitivity to ethanol, cocaine and methamphetamine.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  37
D4 receptor knockout mice exhibit a decrease in novelty-related exploration.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  6
D4 receptor knockout mice exhibit increased avoidance behaviour to unconditioned stimuli.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  9
D4 receptor knockout mice exhibit dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  27
D4 knockout mice exhibit increased co-ordination.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  37
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Drd4tm1(IL2RA)Tao Drd4tm1(IL2RA)Tao/Drd4tm1(IL2RA)Tao
involves: C57BL/6J
MGI:94926  MP:0003463 abnormal single cell response PMID: 14684868 
Drd4tm1Dkg Drd4tm1Dkg/Drd4tm1Dkg
involves: 129P2/OlaHsd * C57BL/6J
MGI:94926  MP:0001417 decreased exploration in new environment PMID: 10531457 
Drd4tm1Dkg Drd4tm1Dkg/Drd4tm1Dkg
involves: 129P2/OlaHsd * C57BL/6J
MGI:94926  MP:0002757 decreased vertical activity PMID: 9323127 
Drd4tm1Dkg Drd4tm1Dkg/Drd4tm1Dkg
involves: 129P2/OlaHsd * C57BL/6J
MGI:94926  MP:0009754 enhanced behavioral response to cocaine PMID: 9323127 
Drd4tm1Dkg Drd4tm1Dkg/Drd4tm1Dkg
involves: 129P2/OlaHsd * C57BL/6J
MGI:94926  MP:0003858 enhanced coordination PMID: 9323127 
Drd4tm1Dkg Drd4tm1Dkg/Drd4tm1Dkg
involves: 129P2/OlaHsd * C57BL/6J
MGI:94926  MP:0002629 hyperactivity elicited by ethanol administration PMID: 9323127 
Drd4tm1Dkg Drd4tm1Dkg/Drd4tm1Dkg
involves: 129P2/OlaHsd * C57BL/6J
MGI:94926  MP:0001402 hypoactivity PMID: 9323127 
Drd4tm1Dkg Drd4tm1Dkg/Drd4tm1Dkg
involves: 129P2/OlaHsd * C57BL/6J
MGI:94926  MP:0009750 impaired behavioral response to addictive substance PMID: 9323127 
Drd4tm1Dkg Drd4tm1Dkg/Drd4tm1Dkg
involves: 129P2/OlaHsd * C57BL/6J
MGI:94926  MP:0001906 increased dopamine level PMID: 9323127 
Biologically Significant Variants
Type:  Repeat polymorphism of Exon III
Species:  Human
Description:  DRD4 7-repeat allele may increase likelihood of ADHD.
References:  8,46
General Comments
Human and primate receptors have a variable number (2-10) of imperfect 48 bp repeats in exon 3 [20,53]. This leads to a highly variable length and aa composition of the putative third cytoplasmic loop, apparently not associated with any marked variation in pharmacology. Most D4 receptor-antagonists display agonistic activities in some heterologous expression systems [11-12].
Available Assays
DiscoveRx PathHunter® CHO-K1 DRD4 β-Arrestin Cell Line (Cat no. 93-0690C2)
PathHunter® eXpress DRD4 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0690E2CP0M)
more info

References

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1. Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH. (1995) Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem65: 1157-1165. [PMID:7643093]

2. Auerbach SS, DrugMatrix® and ToxFX® Coordinator National Toxicology Program. National Toxicoligy Program: Dept of Health and Human Services. Accessed on 02/05/2014. Modified on 02/05/2014. DrugMatrix, https://ntp.niehs.nih.gov/drugmatrix/index.html

3. Chemel BR, Roth BL, Armbruster B, Watts VJ, Nichols DE. (2006) WAY-100635 is a potent dopamine D4 receptor agonist. Psychopharmacology (Berl)188: 244-251. [PMID:16915381]

4. Chio CL, Drong RF, Riley DT, Gill GS, Slighton JL, Huff RM. (1994) D4 dopamine receptor-mediated signalling events determined in transfected Chinese hamster ovary cells. J. Biol. Chem.269: 11813-11819. [PMID:7512953]

5. Cohen AI, Todd RD, Harmon S, O'Malley KL. (1992) Photoreceptors of mouse retinas possess D4 receptors coupled to adenylate cyclase. Proc Natl Acad Sci U S A89: 12093-12097. [PMID:1334557]

6. Dulawa SC, Grandy DK, Low MJ, Paulus MP, Geyer MA. (1999) Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. J. Neurosci.19: 9550-9556. [PMID:10531457]

7. Durcan MJ, Rigdon GC, Norman MH, Morgan PF. (1995) Is clozapine selective for the dopamine D4 receptor?. Life Sci57: PL275-PL283. [PMID:7475902]

8. El-Faddagh M, Laucht M, Maras A, Vöhringer L, Schmidt MH. (2004) Association of dopamine D4 receptor (DRD4) gene with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community sample: a longitudinal study from birth to 11 years of age. J Neural Transm111: 883-889. [PMID:15206004]

9. Falzone TL, Gelman DM, Young JI, Grandy DK, Low MJ, Rubinstein M. (2002) Absence of dopamine D4 receptors results in enhanced reactivity to unconditioned, but not conditioned, fear. Eur J Neurosci15: 158-164. [PMID:11860516]

10. Fishburn CS, Carmon S, Fuchs S. (1995) Molecular cloning and characterisation of the gene encoding the murine D4 dopamine receptor. FEBS Lett.361: 215-219. [PMID:7698326]

11. Gazi L, Bobirnac I, Danzeisen M, Schüpbach E, Bruinvels AT, Geisse S, Sommer B, Hoyer D, Tricklebank M, Schoeffter P. (1998) The agonist activities of the putative antipsychotic agents, L-745,870 and U-101958 in HEK293 cells expressing the human dopamine D4.4 receptor. Br. J. Pharmacol.124: 889-896. [PMID:9692773]

12. Gazi L, Bobirnac I, Danzeisen M, Schüpbach E, Langenegger D, Sommer B, Hoyer D, Tricklebank M, Schoeffter P. (1999) Receptor density as a factor governing the efficacy of the dopamine D4 receptor ligands, L-745,870 and U-101958 at human recombinant D4.4 receptors expressed in CHO cells. Br. J. Pharmacol.128: 613-620. [PMID:10516640]

13. Gazi L, Schoeffter P, Nunn C, Croskery K, Hoyer D, Feuerbach D. (2000) Cloning, expression, functional coupling and pharmacological characterization of the rat dopamine D4 receptor. Naunyn Schmiedebergs Arch Pharmacol361: 555-564. [PMID:10832611]

14. Glavin GB, Hall AM. (1994) Clozapine, a dopamine DA4 receptor antagonist, reduces gastric acid secretion and stress-induced gastric mucosal injury. Life Sci54: PL261-PL264. [PMID:8152334]

15. Hidaka K, Matsumoto M, Tada S, Tasaki Y, Yamaguchi T. (1995) Differential effects of [3H]nemonapride and [3H]spiperone binding on human dopamine D4 receptors. Neurosci. Lett.186 (2-3): 145-8. [PMID:7777184]

16. Kortagere S, Gmeiner P, Weinstein H, Schetz JA. (2004) Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common receptor microdomain. Mol Pharmacol66: 1491-1499. [PMID:15448188]

17. Kulagowski JJ, Broughton HB, Curtis NR, Mawer IM, Ridgill MP, Baker R, Emms F, Freedman SB, Marwood R, Patel S et al.. (1996) 3-((4-(4-Chlorophenyl)piperazin-1-yl)-methyl)-1H-pyrrolo-2,3-b-pyridine: an antagonist with high affinity and selectivity for the human dopamine D4 receptor. J. Med. Chem.39 (10): 1941-2. [PMID:8642550]

18. Lahti RA, Evans DL, Stratman NC, Figur LM. (1993) Dopamine D4 versus D2 receptor selectivity of dopamine receptor antagonists: possible therapeutic implications. Eur J Pharmacol236: 483-486. [PMID:8102973]

19. Lanau F, Zenner MT, Civelli O, Hartman DS. (1997) Epinephrine and norepinephrine act as potent agonists at the recombinant human dopamine D4 receptor. J Neurochem68: 804-812. [PMID:9003072]

20. Livak KJ, Rogers J, Lichter JB. (1995) Variability of dopamine D4 receptor (DRD4) gene sequence within and among nonhuman primate species. Proc. Natl. Acad. Sci. U.S.A.92: 427-431. [PMID:7831304]

21. McAllister G, Knowles MR, Ward-Booth SM, Sinclair HA, Patel S, Marwood R, Emms F, Patel S, Smith A, Seabrook GR. (1995) Functional coupling of human D2, D3, and D4 dopamine receptors in HEK293 cells. J Recept Signal Transduct Res15: 267-281. [PMID:8903944]

22. Meador-Woodruff JH, Damask SP, Wang J, Haroutunian V, Davis KL, Watson SJ. (1996) Dopamine receptor mRNA expression in human striatum and neocortex. Neuropsychopharmacology15: 17-29. [PMID:8797188]

23. Mei YA, Griffon N, Buquet C, Martres MP, Vaudry H, Schwartz JC, Sokoloff P, Cazin L. (1995) Activation of dopamine D4 receptor inhibits an L-type calcium current in cerebellar granule cells. Neuroscience68: 107-116. [PMID:7477916]

24. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A. (2002) Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther303: 791-804. [PMID:12388666]

25. Moreland RB, Patel M, Hsieh GC, Wetter JM, Marsh K, Brioni JD. (2005) A-412997 is a selective dopamine D4 receptor agonist in rats. Pharmacol Biochem Behav82: 140-147. [PMID:16153699]

26. Mulcrone J, Kerwin RW. (1997) The regional pattern of D4 gene expression in human brain. Neurosci Lett234: 147-150. [PMID:9364519]

27. Nir I, Harrison JM, Haque R, Low MJ, Grandy DK, Rubinstein M, Iuvone PM. (2002) Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors. J Neurosci22: 2063-2073. [PMID:11896146]

28. O'Malley KL, Harmon S, Tang L, Todd RD. (1992) The rat dopamine D4 receptor sequence, gene structure, and demonstration of expression in the cardiovascular system. New Biol.2: 137-146. [PMID:1554689]

29. Patel S, Freedman S, Chapman KL, Emms F, Fletcher AE, Knowles M, Marwood R, McAllister G, Myers J, Curtis N, Kulagowski JJ, Leeson PD, Ridgill M, Graham M, Matheson S, Rathbone D, Watt AP, Bristow LJ, Rupniak NM, Baskin E, Lynch JJ, Ragan CI. (1997) Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor. J Pharmacol Exp Ther283: 636-647. [PMID:9353380]

30. Patel S, Patel S, Marwood R, Emms F, Marston D, Leeson PD, Curtis NR, Kulagowski JJ, Freedman SB. (1996) Identification and pharmacological characterization of [125I]L-750,667, a novel radioligand for the dopamine D4 receptor. Mol Pharmacol50: 1658-1664. [PMID:8967990]

31. Pilla M, Perachon S, Sautel F, Garrido F, Mann A, Wermuth CG, Schwartz JC, Everitt BJ, Sokoloff P. (1999) Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature400: 371-375. [PMID:10432116]

32. Pillai G, Brown NA, McAllister G, Milligan G, Seabrook GR. (1998) Human D2 and D4 dopamine receptors couple through betagamma G-protein subunits to inwardly rectifying K+ channels (GIRK1) in a Xenopus oocyte expression system: selective antagonism by L-741,626 and L-745,870 respectively. Neuropharmacology37: 983-987. [PMID:9833627]

33. Primus RJ, Thurkauf A, Xu J, Yevich E, McInerney S, Shaw K, Tallman JF, Gallagher DW. (1997) II. Localization and characterization of dopamine D4 binding sites in rat and human brain by use of the novel, D4 receptor-selective ligand [3H]NGD 94-1. J. Pharmacol. Exp. Ther.282 (2): 1020-7. [PMID:9262371]

34. Ricci A, Mignini F, Tomassoni D, Amenta F. (2006) Dopamine receptor subtypes in the human pulmonary arterial tree. Auton Autacoid Pharmacol26: 361-369. [PMID:16968475]

35. Rivera A, Trías S, Penafiel A, Angel Narváez J, Díaz-Cabiale Z, Moratalla R, de la Calle A. (2003) Expression of D4 dopamine receptors in striatonigral and striatopallidal neurons in the rat striatum. Brain Res989: 35-41. [PMID:14519509]

36. Rowley M, Broughton HB, Collins I, Baker R, Emms F, Marwood R, Patel S, Patel S, Ragan CI, Freedman SB et al.. (1996) 5-(4-Chlorophenyl)-4-methyl-3-(1-(2-phenylethyl)piperidin-4-yl)isoxazole: a potent, selective antagonist at human cloned dopamine D4 receptors. J. Med. Chem.39 (10): 1943-5. [PMID:8642551]

37. Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA, Saez C, Pugsley TA, Gershanik O, Low MJ, Grandy DK. (1997) Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell90: 991-1001. [PMID:9323127]

38. Schetz JA, Benjamin PS, Sibley DR. (2000) Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology. Mol Pharmacol57: 144-152. [PMID:10617689]

39. Schlachter SK, Poel TJ, Lawson CF, Dinh DM, Lajiness ME, Romero AG, Rees SA, Duncan JN, Smith MW. (1997) Substituted 4-aminopiperidines having high in vitro affinity and selectivity for the cloned human dopamine D4 receptor. Eur J Pharmacol322: 283-286. [PMID:9098699]

40. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE. (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl)124: 57-73. [PMID:8935801]

41. Seeman P, Guan HC, Van Tol HH, Niznik HB. (1993) Low density of dopamine D4 receptors in Parkinson's, schizophrenia, and control brain striata. Synapse14: 247-253. [PMID:8248849]

42. Shih YH, Chung FZ, Pugsley TA. (1997) Cloning, expression and characterization of a human dopamine D4.2 receptor (CHO K1 cells) and various D4.2/D2L chimeras (COS-7 cells). Prog Neuropsychopharmacol Biol Psychiatry21: 153-167. [PMID:9075264]

43. Shin Y, Kumar U, Patel Y, Patel SC, Sidhu A. (2003) Differential expression of D2-like dopamine receptors in the kidney of the spontaneously hypertensive rat. J Hypertens21: 199-207. [PMID:12544452]

44. Skaaning Jensen B, Levavi-Sivan B, Fishburn CS, Fuchs S. (1997) Functional expression of the murine D2, D3, and D4 dopamine receptors in Xenopus laevis oocytes. FEBS Lett420: 191-195. [PMID:9459308]

45. Sun D, Wilborn TW, Schafer JA. (1998) Dopamine D4 receptor isoform mRNA and protein are expressed in the rat cortical collecting duct. Am J Physiol275: F742-F751. [PMID:9815131]

46. Sunohara GA, Roberts W, Malone M, Schachar RJ, Tannock R, Basile VS, Wigal T, Wigal SB, Schuck S, Moriarty J, Swanson JM, Kennedy JL, Barr CL. (2000) Linkage of the dopamine D4 receptor gene and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry39: 1537-1542. [PMID:11128331]

47. Suzuki T, Kobayashi K, Nagatsu T. (1995) Genomic structure and tissue distribution of the mouse dopamine D4 receptor. Neurosci Lett199: 69-72. [PMID:8584230]

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How to cite this page

Arvid Carlsson, Marc G. Caron, Olivier Civelli, John W. Kebabian, Saloman Z. Langer, Bernard Scatton, Jean-Charles Schwartz, Goran Sedvall, Philip Seeman, Pierre Sokoloff, Pierre F. Spano, Hubert H. M. Van Tol.
Dopamine receptors: D4 receptor. Last modified on 11/06/2014. Accessed on 22/10/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=217.