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D4 receptor

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Target not currently curated in GtoImmuPdb

Target id: 217

Nomenclature: D4 receptor

Family: Dopamine receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 419 11p15.5 DRD4 dopamine receptor D4 74
Mouse 7 387 7 86.6 cM Drd4 dopamine receptor D4 41
Rat 7 387 1q41 Drd4 dopamine receptor D4 17
Previous and Unofficial Names Click here for help
d(2C) dopamine receptor | dopamine receptor 4 | D4R
Database Links Click here for help
Specialist databases
GPCRDB drd4_human (Hs), drd4_mouse (Mm), drd4_rat (Rn)
Other databases
Alphafold P21917 (Hs), P51436 (Mm), P30729 (Rn)
ChEMBL Target CHEMBL219 (Hs), CHEMBL2574 (Mm), CHEMBL3361 (Rn)
DrugBank Target P21917 (Hs)
Ensembl Gene ENSG00000069696 (Hs), ENSMUSG00000025496 (Mm), ENSRNOG00000017927 (Rn)
Entrez Gene 1815 (Hs), 13491 (Mm), 25432 (Rn)
Human Protein Atlas ENSG00000069696 (Hs)
KEGG Gene hsa:1815 (Hs), mmu:13491 (Mm), rno:25432 (Rn)
OMIM 126452 (Hs)
Pharos P21917 (Hs)
RefSeq Nucleotide NM_000797 (Hs), NM_007878 (Mm), NM_012944 (Rn)
RefSeq Protein NP_000788 (Hs), NP_031904 (Mm), NP_037076 (Rn)
UniProtKB P21917 (Hs), P51436 (Mm), P30729 (Rn)
Wikipedia DRD4 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human D4 Dopamine receptor in complex with Nemonapride
PDB Id:  5WIU
Ligand:  nemonapride
Resolution:  1.96Å
Species:  Human
References:  77
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the sodium-bound human D4 Dopamine receptor in complex with Nemonapride
PDB Id:  5WIV
Ligand:  nemonapride
Resolution:  2.14Å
Species:  Human
References:  77
Natural/Endogenous Ligands Click here for help
dopamine

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CP-226269 Small molecule or natural product Rn Partial agonist 9.4 pKi 26
⤷ pKi 9.4 [26]
FAUC213 Small molecule or natural product Rn Partial agonist 9.0 pKi 26
⤷ pKi 9.0 [26]
PD168,077 Small molecule or natural product Rn Partial agonist 8.8 pKi 26
⤷ pKi 8.8 (Ki 1.58x10-9 M) [26]
apomorphine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 8.4 pKi 36
⤷ pKi 8.4 [36]
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 8.3 pKi 36
⤷ pKi 8.3 [36]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 8.2 pKi 36
⤷ pKi 8.2 [36]
A412997 Small molecule or natural product Rn Agonist 8.1 pKi 37
⤷ pKi 8.1 (Ki 7.9x10-9 M) [37]
A412997 Small molecule or natural product Hs Full agonist 8.1 pKi 37
⤷ pKi 8.1 (Ki 7.9x10-9 M) [37]
WAY-100635 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.8 pKi 1
⤷ pKi 7.8 (Ki 1.6x10-8 M) [1]
dopamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 7.6 pKi 74
⤷ pKi 7.6 [74]
quinpirole Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.5 pKi 36,44,74
⤷ pKi 7.5 [36,44,74]
dopamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Rn Full agonist 7.4 pKi 53
⤷ pKi 7.4 [53]
cabergoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.3 pKi 36
⤷ pKi 7.3 [36]
rotigotine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.3 pKi 76
⤷ pKi 7.3 (Ki 5.5x10-8 M) [76]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.2 pKi 36
⤷ pKi 7.2 [36]
fenoldopam Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 6.5 pKi 74
⤷ pKi 6.5 [74]
ABT-670 Small molecule or natural product Primary target of this compound Hs Full agonist 5.8 pKi 42
⤷ pKi 5.8 (Ki 1.445x10-6 M) [42]
PF-592379 Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.4 pIC50 12
⤷ pIC50 5.4 (IC50 4.165x10-6 M) [12]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
nemonapride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 10.0 pKd 59
⤷ pKd 10.0 [59]
[125I]L750667 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.8 pKd 44
⤷ pKd 9.8 (Kd 1.6x10-10 M) [44]
[3H]spiperone Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Antagonist 9.5 pKd 24,74
⤷ pKd 9.5 (Kd 3x10-10 M) [24,74]
[3H]NGD941 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.3 pKd 47
⤷ pKd 8.3 (Kd 5x10-9 M) [47]
benperidol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 10.2 pKi 60
⤷ pKi 10.2 (Ki 6.6x10-11 M) [60]
perospirone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 10.1 pKi 60
⤷ pKi 10.1 (Ki 9x10-11 M) [60]
L-750,667 Small molecule or natural product Rn Antagonist 10.0 pKi 53
⤷ pKi 10.0 [53]
RBI257 Small molecule or natural product Rn Antagonist 9.6 pKi 26
⤷ pKi 9.6 [26]
[3H]N-methylspiperone Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Antagonist 9.5 pKi 53
⤷ pKi 9.5 [53]
CP-293019 Small molecule or natural product Rn Antagonist 9.5 pKi 26
⤷ pKi 9.5 [26]
NGD 94-1 Small molecule or natural product Rn Antagonist 9.5 pKi 26
⤷ pKi 9.5 [26]
L745870 Small molecule or natural product Ligand has a PDB structure Hs Antagonist 9.4 pKi 28
⤷ pKi 9.4 (Ki 3.9x10-10 M) [28]
spiperone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.3 pKi 14
⤷ pKi 9.3 [14]
FAUC213 Small molecule or natural product Rn Antagonist 9.0 pKi 26
⤷ pKi 9.0 [26]
sonepiprazole Small molecule or natural product Hs Antagonist 8.9 pKi 54
⤷ pKi 8.9 (Ki 1.4x10-9 M) [54]
U101958 Small molecule or natural product Hs Antagonist 8.9 pKi 54
⤷ pKi 8.9 (Ki 1.4x10-9 M) [54]
A-381393 Small molecule or natural product Primary target of this compound Hs Antagonist 8.8 pKi 39
⤷ pKi 8.8 (Ki 1.5x10-9 M) [39]
haloperidol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.7 – 8.8 pKi 29,61,73
⤷ pKi 8.7 – 8.8 [29,61,73]
sonepiprazole Small molecule or natural product Rn Antagonist 8.7 pKi 26
⤷ pKi 8.7 [26]
L741742 Small molecule or natural product Hs Antagonist 8.5 pKi 51
⤷ pKi 8.5 (Ki 3.16x10-9 M) [51]
sertindole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.8 – 9.1 pKi 7,57-58,60
⤷ pKi 7.8 – 9.1 (Ki 1.6x10-8 – 8.5x10-10 M) [7,57-58,60]
loxapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.1 pKi 58
⤷ pKi 8.1 (Ki 7.8x10-9 M) [58]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.1 pKi 36
⤷ pKi 8.1 [36]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.8 pKi 29
⤷ pKi 7.8 [29]
Ro 10-4548 Small molecule or natural product Rn Antagonist 7.8 pKi 26
⤷ pKi 7.8 [26]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.5 pKi 29
⤷ pKi 7.5 [29]
ML398 Small molecule or natural product Primary target of this compound Hs Antagonist 7.4 pKi 6
⤷ pKi 7.4 (Ki 3.6x10-8 M) [6]
zotepine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.4 pKi 56
⤷ pKi 7.4 (Ki 3.9x10-8 M) [56]
trifluoperazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.4 pKi 58
⤷ pKi 7.4 (Ki 4.4x10-8 M) [58]
aripiprazole Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.3 pKi 53
⤷ pKi 7.3 [53]
eticlopride Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 pKi 14
⤷ pKi 7.0 [14]
(-)-sulpiride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.7 – 7.7 pKi 44,70
⤷ pKi 5.7 – 7.7 (Ki 1.9x10-6 – 2x10-8 M) [44,70]
piribedil Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.5 pKi 36
⤷ pKi 6.5 [36]
bromocriptine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.4 pKi 36
⤷ pKi 6.4 [36]
nafadotride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.4 pKi 53
⤷ pKi 6.4 [53]
(+)-butaclamol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.3 pKi 44
⤷ pKi 6.3 [44]
prochlorperazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.1 pKi 3
⤷ pKi 6.1 (Ki 8.1x10-7 M) [3]
raclopride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.7 pKi 53
⤷ pKi 5.7 [53]
(+)-sulpiride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.7 pKi 44
⤷ pKi 5.7 (Ki 2.2x10-6 M) [44]
View species-specific antagonist tables
Immuno Process Associations
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0099149 regulation of postsynaptic neurotransmitter receptor internalization IEA
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
References:  45
Tissue Distribution Click here for help
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:  38
Brain: Pre-frontal cortex, temporal neocortex > occipital cortex.
Species:  Human
Technique:  in situ hybridization.
References:  34
Aortic endothelium, umbilical vein endothelium.
Species:  Human
Technique:  RT-PCR
References:  80
Pulmonary artery.
Species:  Human
Technique:  Western Blot and Immunohistochemistry.
References:  48
Brain (especially cerebellum), eye, adrenal gland, testes, superior cervical ganglion, submaxillary gland, pancreas.
Species:  Mouse
Technique:  RT-PCR
References:  67
Retina, photoreceptor cell layer and inner nuclear and ganglion cell layers.
Species:  Mouse
Technique:  RT-PCR and in situ hybridization.
References:  11
Motor, somatosensory, visual, auditory, temporal association, cingulate, retrosplenial and granular insular cortices.
Species:  Rat
Technique:  Immunohistochemistry.
References:  49
Kidney: Cortical collecting duct.
Species:  Rat
Technique:  RT-PCR
References:  65
Striatum, substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus.
Species:  Rat
Technique:  Immunohistochemistry.
References:  50
Nucleus accumbens shell.
Species:  Rat
Technique:  immunocytochemistry.
References:  68
Pineal gland.
Species:  Rat
Technique:  RT-PCR.
References:  25
Kidney: Cortex > inner medulla.
Species:  Rat
Technique:  Western Blot and Immunocytochemistry.
References:  63
Expression Datasets Click here for help

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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 Click here for help
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:  8,18,32
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:  2,10,30,43,62,69
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:  2
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:  20
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:  35
Measurement of mitogenesis in CHO cells transfected with the human D4 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Mitogenesis.
References:  54
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:  64
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:  46,78
Recruitment of beta-arrestin.
Species:  Human
Tissue:  Transfected CHO and HEK293 cells.
Response measured: 
References:  5,27,33
Physiological Functions Click here for help
Modulation of the dark level of light-sensitive cAMP in photoreceptors.
Species:  Mouse
Tissue:  Retina.
References:  11
Regulation of electrolyte and water transport.
Species:  Rat
Tissue:  Kidney.
References:  63,65
Modulation of von Willebrand factor secretion in endothelial cells.
Species:  Human
Tissue:  Endothelium.
References:  80
Modulation of gastric acid secretion.
Species:  Rat
Tissue:  In vivo.
References:  21
Modulation of AMPA receptor trafficking and functions.
Species:  Rat
Tissue:  Prefrontal cortex.
References:  79
Modulation of angiotensin II type 1 receptor expression.
Species:  Rat
Tissue:  Kidney.
References:  9
Modulation of neuronal electrophysiological properties.
Species:  Mouse
Tissue:  Prefrontal cortex.
References:  81
Modulation of GABAA receptor functions.
Species:  Rat
Tissue:  Prefrontal cortex primary neurons.
References:  23
Physiological Consequences of Altering Gene Expression Click here for help
D4 receptor knockout mice exhibit increased avoidance behaviour to unconditioned stimuli.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  16
D4 receptor knockout mice exhibit an increased sensitivity to ethanol, cocaine and methamphetamine.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  52
D4 receptor knockout mice exhibit a decrease in novelty-related exploration.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  13
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:  40
D4 receptor knockout mice exhibit increased co-ordination.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  52
D4 receptor knockout mice exhibit reduced longevity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells and genotype polymorphism.
References:  22
D4 receptor knockout mice exhibit an increase in blood pressure.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells and genotype polymorphism.
References:  4
D4 receptor knockout mice exhibit an increase in glutamate extracellular levels.
Species:  Mouse
Tissue:  Striatum.
Technique:  Gene targeting in embryonic stem cells and genotype polymorphism.
References:  71
D4 receptor knockout mice exhibit a decrease in dopamine release.
Species:  Mouse
Tissue:  Striatum.
Technique:  Gene targeting in embryonic stem cells and genotype polymorphism.
References:  72
Phenotypes, Alleles and Disease Models Click here for help 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 Click here for help
Type:  Repeat polymorphism of Exon III
Species:  Human
Description:  DRD4 7-repeat allele may increase likelihood of ADHD.
References:  15,66
General Comments
Human and primate receptors have a variable number (2-10) of imperfect 48 bp repeats in exon 3 [31,75]. This leads to a highly variable length and amino acid composition of the putative third cytoplasmic loop, apparently not associated with any marked variation in pharmacology. In humans the D4.2, D4.4 and D4.7 variants are the predominant variants [55].

Most D4 receptor-antagonists display agonistic activities in some heterologous expression systems [18-19].

References

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1. Al Hussainy R, Verbeek J, van der Born D, Braker AH, Leysen JE, Knol RJ, Booij J, Herscheid JK. (2011) Design, synthesis, radiolabeling, and in vitro and in vivo evaluation of bridgehead iodinated analogues of N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamide (WAY-100635) as potential SPECT ligands for the 5-HT1A receptor. J Med Chem, 54 (10): 3480-91. [PMID:21520940]

2. 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 Neurochem, 65 (3): 1157-65. [PMID:7643093]

3. Auerbach SS, DrugMatrix® and ToxFX® Coordinator National Toxicology Program. National Toxicology 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

4. Bek MJ, Wang X, Asico LD, Jones JE, Zheng S, Li X, Eisner GM, Grandy DK, Carey RM, Soares-da-Silva P et al.. (2006) Angiotensin-II type 1 receptor-mediated hypertension in D4 dopamine receptor-deficient mice. Hypertension, 47 (2): 288-95. [PMID:16380537]

5. Bergman J, Roof RA, Furman CA, Conroy JL, Mello NK, Sibley DR, Skolnick P. (2013) Modification of cocaine self-administration by buspirone (buspar®): potential involvement of D3 and D4 dopamine receptors. Int J Neuropsychopharmacol, 16 (2): 445-58. [PMID:22827916]

6. Berry CB, Bubser M, Jones CK, Hayes JP, Wepy JA, Locuson CW, Daniels JS, Lindsley CW, Hopkins CR. (2014) Discovery and Characterization of ML398, a Potent and Selective Antagonist of the D4 Receptor with in Vivo Activity. ACS Med Chem Lett, 5 (9): 1060-4. [PMID:25221667]

7. Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, Nash NR, Olsson R, Davis RE, Hacksell U et al.. (2005) Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J Pharmacol Exp Ther, 315 (3): 1278-87. [PMID:16135699]

8. Chemel BR, Roth BL, Armbruster B, Watts VJ, Nichols DE. (2006) WAY-100635 is a potent dopamine D4 receptor agonist. Psychopharmacology (Berl.), 188 (2): 244-51. [PMID:16915381]

9. Chen K, Deng K, Wang X, Wang Z, Zheng S, Ren H, He D, Han Y, Asico LD, Jose PA et al.. (2015) Activation of D4 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells. Hypertension, 65 (1): 153-60. [PMID:25368031]

10. Chio CL, Drong RF, Riley DT, Gill GS, Slightom JL, Huff RM. (1994) D4 dopamine receptor-mediated signaling events determined in transfected Chinese hamster ovary cells. J Biol Chem, 269 (16): 11813-9. [PMID:7512953]

11. 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 USA, 89 (24): 12093-7. [PMID:1334557]

12. Collins GT, Butler P, Wayman C, Ratcliffe S, Gupta P, Oberhofer G, Caine SB. (2012) Lack of abuse potential in a highly selective dopamine D3 agonist, PF-592,379, in drug self-administration and drug discrimination in rats. Behav Pharmacol, 23 (3): 280-91. [PMID:22470105]

13. 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 (21): 9550-6. [PMID:10531457]

14. Durcan MJ, Rigdon GC, Norman MH, Morgan PF. (1995) Is clozapine selective for the dopamine D4 receptor?. Life Sci, 57 (18): PL275-83. [PMID:7475902]

15. 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 Transm (Vienna), 111 (7): 883-9. [PMID:15206004]

16. 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 Neurosci, 15 (1): 158-64. [PMID:11860516]

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