D4 Receptor
The dopamine D4 receptor (D4R) is a G protein-coupled receptor (GPCR) primarily involved in modulating dopaminergic signaling in the prefrontal cortex and limbic regions[1][2]. Mechanistically, D4R influences cognitive processes and gamma oscillatory activity through interactions with parvalbumin-expressing interneurons and the neuregulin/ErbB4 pathway[3]. Distinct from the D2 and D3 receptor subtypes, D4R exhibits limited brain distribution, which supports its specialized role in executive function and behavioral flexibility[4][3]. Genetic polymorphisms of DRD4, including the 2-repeat and 7-repeat variants, alter receptor responsiveness and are associated with neuropsychiatric conditions such as ADHD and mood disorders[5][6][7]. In disease models, D4R activity has been implicated in schizophrenia-related cognitive deficits, with selective antagonists showing limited efficacy on positive symptoms but potential effects on cognition[3][8]. D4R also mediates behavioral responses relevant to substance use, particularly in relapse to stimulants, highlighting its importance in addiction research[4]. Compared with related isoforms, D4R demonstrates unique patterns of ubiquitination that may modulate receptor trafficking and signaling without inducing degradation[5]. These features make D4R a viable target for experimental modulation using selective agonists and antagonists in both in vitro and in vivo studies[9][4].
References:
- [1]. Helmeste DM, et al. Dopamine D4 receptors. Jpn J Pharmacol. 2000 Jan;82(1):1-14. [Content Brief]
- [2]. Reynolds G, et al. Are there detectable D4 receptors in the brain in schizophrenia. Schizophr Res. 1995;15:69.
- [3]. Furth KE, et al. Dopamine, cognitive function, and gamma oscillations: role of D4 receptors. Front Cell Neurosci. 2013 Jul 2;7:102. [Content Brief]
- [4]. Di Ciano P, et al. Dopamine D4 receptors in psychostimulant addiction. Adv Pharmacol. 2014;69:301-21. [Content Brief]
- [5]. Skieterska K, et al. Dopamine D4 receptor ubiquitination. Biochem Soc Trans. 2016 Apr 15;44(2):601-5. [Content Brief]
- [6]. Leung PW, et al. Dopamine receptor D4 (DRD4) gene in Han Chinese children with attention-deficit/hyperactivity disorder (ADHD): increased prevalence of the 2-repeat allele. Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):54-6. [Content Brief]
- [7]. Macciardi F, et al. The D4 receptor gene and mood disorders: an association study. Am J Hum Genet. 1994;55:A336.
- [8]. Kramer MS, et al. The effects of a selective D4 dopamine receptor antagonist (L-745,870) in acutely psychotic inpatients with schizophrenia. D4 Dopamine Antagonist Group. Arch Gen Psychiatry. 1997 Jun;54(6):567-72. [Content Brief]
- [9]. Ptáček R, et al. Targeted D4 dopamine receptors: implications for drug discovery and therapeutic development. Curr Drug Targets. 2013 Apr;14(4):507-12. [Content Brief]
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D4 Receptor Related Products (92)
Related Products (92)
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L 741742 hydrochloride
0 ImagesCat. No.: HY-101349ACAS No.: 874882-93-6L 741742 hydrochloride is a highly selective and brain-penetrant D4 dopamine receptor antagonist, with Ki values of 3.5 nM, 770 nM and >1700 nM for human D4, D3 and D2 receptors, respectively. L 741742 hydrochloride suppresses PDGFRβ, ERK1/2, and mTOR signaling pathways, and impairs autophagic flux while disrupting lysosomal function.L 741742 hydrochloride induces G0/G1 cell-cycle arrest and apoptosis, promotes neuronal differentiation of normal human neural stem cells, selectively inhibits growth and clonogenic potential of glioblastoma neural stem cells and primary glioblastoma tumor cells, exerts synergistic effects with Temozolomide (TMZ) (HY-17364) against glioblastoma neural stem cells in vitro, and inhibits glioblastoma neural stem cell xenograft growth in immunocompromised mice. L 741742 hydrochloride can be used for the research of schizophrenia and glioblastoma.
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L-745870 trihydrochloride
0 ImagesCat. No.: HY-14325ACAS No.: 866021-03-6L-745870 trihydrochloride is a potent, selective, brain-penetrant and orally active dopamine D4 receptor antagonist with a Ki of 0.43 nM. L-745870 trihydrochloride shows weaker affinity for D2 (Ki of 960 nM) and D3 (Ki of 2300 nM) receptors, and exhibits moderate affinity for 5-HT2 receptors, sigma sites and α-adrenoceptors.
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SV 156
0 ImagesCat. No.: HY-111242CAS No.: 873445-60-4SV 156 is a potent and selective D2 dopamine receptor antagonist, with a Ki of 2.5 nM for hD2. SV 156 has approximately 40-fold binding selectivity for D2 dopamine receptors compared to the D3 receptor subtype. SV 156 can be used for L-DOPA (HY-N0304)-associated abnormal involuntary movements (AIMs) research.
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FMJ-01-054
0 ImagesCat. No.: HY-181049FMJ-01-054 is a selective dopamine D4 Receptor (D4R) antagonist with a Ki od 77.7 nM. FMJ-01-054 shows subtype selectivity over D2R and D3R. FMJ-01-054 inhibits D4R-mediated β-arrestin recruitment and cAMP production with IC50 values of 3800 nM and 134 nM, respectively. FMJ-01-054 has desirable plasma half-life and brain exposure in rats. FMJ-01-054 can be used for the research of neurological disorders.
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Raclopride tartrate
0 ImagesCat. No.: HY-108976CAS No.: 98185-20-7Raclopride tartrate is a selective dopamine D2/D3 receptor antagonist with potential antipsychotic effects. Raclopride tartrate binds to D2 and D3 receptors with Kis of 1.8 nM and 3.5 nM, respectively.
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Mazapertine
0 ImagesMazapertine is an orally active antipsychotic agent. M azapertine antagonizes to dopamine D2/3/4 receptors (Ki values < 3 nM) and also strongly binds to serotonin 5-HT1A receptor (Ki =1.7 nM) and α1-adrenergic receptor (Ki = 1.3 nM). Mazapertine can be used for the research of neurological disease.
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Ro 10-5824
0 ImagesCat. No.: HY-101384CAS No.: 189744-46-5Ro 10-5824 is a potent and selective D4R partial agonist with a Ki of 5.2 nM. Ro 10-5824 increases novel object exploration in C57 mice.
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BMY 28674
0 ImagesCat. No.: HY-100057CAS No.: 125481-61-0Synonyms: 6-Hydroxybuspirone; 6'-Hydroxybuspirone; BMS 528215BMY 28674 (6-Hydroxybuspirone) is the active metabolite of the anxiolytic buspirone (HY-B1115A) and is metabolized by CYP3A4.4. BMY 28674 binds to the serotonin (5-HT) receptor subtype 5-HT1A in the rat hippocampus and dorsal raphe (EC50s are 4 and 1 μM, respectively) and is an antagonist of dopamine D2, D3, and D4 receptors (IC50s are 3.1, 4.9, and 0.85 μM, respectively). BMY 28674 also inhibits organic cation transporter 1 (OCT1), OCT2, and OCT3 expressing human transporters in S2 proximal tubule cells in a concentration-dependent manner.
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Asenapine citrate
0 ImagesCat. No.: HY-10121BCAS No.: 1411867-74-7Synonyms: Org 5222 citrateAsenapine citrate, an atypical antipsychotic, is an antagonist of serotonin receptors (pKi: 8.4-10.5), adrenoceptors (pKi: 8.9-9.5), dopamine receptors (pKi: 8.9-9.4) and histamine receptors (pKi: 8.2-9.0). Asenapine citrate can be used in the research of schizophrenia and bipolar disorder.
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Dopamine D4 receptor ligand 2
0 ImagesCat. No.: HY-157563CAS No.: 219125-63-0Dopamine D4 receptor ligand 2 (compound 17) is a potent and selective dopamine D4 ligand with IC50 values of 0.057, >1000, 220, 270 nM for D4, D2, 5-HT1A, α1, respectively.
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PD-143188
0 ImagesCat. No.: HY-19186CAS No.: 150013-70-0Synonyms: CI 1007PD-143188 (CI 1007) is a selective agonist targeting dopamine (DA) receptors, with Ki values of 25.5 nM and 16.6 nM for human D2 and D3 receptors, respectively and lower affinity for D4.2 receptors (Ki=90.9 nM). PD-143188 inhibits DA release, synthesis and metabolism, while reducing cellular cyclic AMP levels, exerting antipsychotic activity. PD-143188 is promising for research of psychopharmacology.
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Loxapine hydrochloride
0 ImagesCat. No.: HY-17390BCAS No.: 54810-23-0Loxapine hydrochloride is an orally active dopamine inhibitor, 5-HT receptor antagonist and also a dibenzoxazepine anti-psychotic agent.
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Asenapine-13C,d3 hydrochloride
0 ImagesCat. No.: HY-16567SSynonyms: Org 5222-13C,d3 hydrochlorideAsenapine-13C,d3 (hydrochloride) is the 13C- and deuterium labeled Asenapine (hydrochloride). Asenapine hydrochloride, an antipsychotic, is a 5-HT (1A, 1B, 2A, 2B, 2C, 5A, 6, 7) and Dopamine (D2, D3, D4) receptor antagonist with Ki values of 0.03-4.0 nM for 5-HT and 1.3, 0.42, 1.1 nM for Dopamine receptor, respectively.
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D4R antagonis-2
0 ImagesCat. No.: HY-145906CAS No.: 2846077-70-9D4R antagonist-2 is a potent and selective D4R antagonist with an IC50 of 6.52 µM. D4R antagonist-2 displays very favorable in vitro PK parameters and has good brain penetration. D4R antagonist-2 has the potential for the research of Parkinson’s disease.
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PD 168568
0 ImagesCat. No.: HY-103407CAS No.: 210688-56-5PD 168568 is a orally active and potent dopamine receptor D4 (DRD4) antagonist. PD 168568 contains an isoindolinone and is selective for the D4 receptor versus D2 and D3, with Ki values of 8.8, 1842, and 2682 nM, respectively. PD 168568 can be used for glioblastoma (GBM) research.
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U-99363E
0 ImagesCat. No.: HY-169136CAS No.: 170856-57-2U-99363E is a selective dopamine D4 receptor antagonist with a Ki value of 2.2 nM. U-99363E exhibits at least 100-fold lower affinity for other dopaminergic, serotonergic and adrenergic receptors. U-99363E can be used in studies related to selective dopamine D4 site labeling or blockade.
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Perphenazine dihydrochloride
0 ImagesPerphenazine dihydrochloride is an orally active dopamine receptor and histamine-1 receptor antagonist, with Ki values of 0.56 nM (D2), 0.43 nM (D3), 6 nM (5-HT2A), respectively. Perphenazine dihydrochloride also binds to Alpha-1A adrenergic receptor. Perphenazine dihydrochloride inhibits cancer cell proliferation, and induces apoptosis. Perphenazine dihydrochloride can be used in the research of mental disease, cancer, inflammation.
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(Rac)-Rotigotine-d7 (hydrochloride)
0 ImagesCat. No.: HY-15394SCAS No.: 3026226-88-7Synonyms: N-0437-d7 (hydrochloride)(Rac)-Rotigotine-d7 (hydrochloride) is deuterium labeled (Rac)-Rotigotine (hydrochloride). (Rac)-Rotigotine hydrochloride is a racemate of Rotigotine. Rotigotine is a full agonist of dopamine receptor, a partial agonist of the 5-HT1A receptor, and an antagonist of the α2B-adrenergic receptor, with Kis of 0.71 nM, 4-15 nM, and 83 nM for the dopamine D3 receptor and D2, D5, D4 receptors, and dopamine D1 receptor.
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FGH31
0 ImagesCat. No.: HY-155099CAS No.: 3033813-47-4FGH31 (Compound 24) is a potent, selective, GRK2 dependency dopamine D4 agonist, with the Ki of 1.6 nM. FGH31 partial activates β- arrestin.
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L-750667 triHydrochloride
0 ImagesL-750667 triHydrochloride is a selective antagonist for the D4 dopamine receptor, with a Ki value of 0.51 nM. The radiolabeled form of L-750667, [125I]L-750,667, has a Kd value of 0.16 nM for the D4 receptor. L-750667 triHydrochloride can reverse dopamine-induced inhibition of cAMP accumulation. It can be used to study the distribution and function of D4 dopamine receptors in the central nervous system and has potential applications in the fields of neuroscience and psychiatry.
