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].
参考文献:
- [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 関連製品 (92)
関連製品 (92)
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Iloperidone
0 Images別名: HP 873Iloperidone (HP 873) is a D2/5-HT2 receptor antagonist. Iloperidone is an atypical antipsychotic for the schizophrenia symptoms.
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UNC9994 hydrochloride
0 ImagesUNC9994 hydrochloride is a functionally selective, β-arrestin–biased dopamine D2 receptor (D2R) agonist that selectively activates β-arrestin recruitment and signaling. UNC9994 hydrochloride shows a binding affinity with a Ki of 79 nM for D2R. UNC9994 hydrochloride is also an antagonist of Gi-regulated cAMP production and partial agonist for D2R/β-arrestin-2 interactions. UNC9994 hydrochloride shows antipsychotic-like activity.
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PD-168077 maleate
0 ImagesPD-168077 maleate is a selective dopamine D4 receptor agonist, with a Ki of 9 nM.
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Pramipexole dihydrochloride hydrate
0 ImagesPramipexole dihydrochloride hydrate is a selective and blood-brain barrier (BBB) penetrant dopamine D2-type receptor agonist, with Kis of 2.2 nM, 3.9 nM, 0.5 nM and 1.3 nM for D2-type receptor, D2, D3 and D4 receptors, respectively. Pramipexole dihydrochloride hydrate can be used for the research of Parkinson's disease (PD) and restless legs syndrome (RLS).
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Asenapine
0 Images別名: Org 5222Asenapine (Org 5222), 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 can be used in the research of schizophrenia and bipolar disorder.
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L-745870 hydrochloride
0 ImagesL-745870 hydrochloride is a potent, selective, brain-penetrant and orally active dopamine D4 receptor antagonist with a Ki of 0.43 nM. L-745870 hydrochloride 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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UCSF924
0 ImagesUCSF924, a chemical probe, is a potent and specific dopamine D4 receptor (DRD4) partial agonist with a EC50 of 4.2 nM. UCSF924 has no off-target effects on more than 320 non-olfactory GPCRs. UCSF924 can be used for research in the field of neuropsychiatric diseases.
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Spiperone hydrochloride
0 ImagesSpiperone hydrochloride (Spiroperidol hydrochloride) is a selective dopamine D2 receptor (Ki values of 0.06 nM, 0.6 nM, 0.08 nM, ~350 nM, ~3500 nM for D2, D3, D4, D1 and D5 receptors, respectively) and 5-HT2A/5-HT1A receptor (Kis of 1 nM/49 nM) antagonist. Spiperone hydrochloride is also a selective α1B-adrenoceptor antagonist. Spiperone hydrochloride activates calcium-activated chloride channel (CaCC). Antipsychotic and anti-inflammatory activities.
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Ecopipam
0 Images別名: SCH 39166Ecopipam (SCH 39166) is a potent, selective and orally active antagonist of dopamine D1/D5 receptor, with Kis of 1.2 nM and 2.0 nM, respectively. Ecopipam shows more than 40-flod selectivity over D2, D4, 5-HT, and α2a receptor (Ki=0.98, 5.52, 0.08, and 0.73 μM, respectively). Ecopipam can be used for the research of schizophrenia and obesity.
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Sarizotan
0 Images別名: EMD 128130Sarizotan (EMD 128130) is an orally active serotonin 5-HT1A receptor and dopamine receptor agonist. Sarizotan (EMD 128130) exhibits IC50 values of 6.5 nM (rat 5-HT1A), 0.1 nM (human 5-HT1A), 15.1 nM (rat D2), 17 nM (human D2), 6.8 nM (human D3) and 2.4 nM (human D4.2), respectively.
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Pipamperone
0 ImagesPipamperone (Floropipamide) is a butyrophenone derivative and high-affinity antagonist of 5-HT2A receptor (pKi=8.2) and D4 receptor (pKi=8.0). Pipamperone is also a low-affinity antagonist of D2 receptor (pKi=6.7). Pipamperone affects neurotransmitter functions and exerts antipsychotic activity. Pipamperone is used in the research of mental disorders such as autism-related behavioral disorders and Alzheimer's disease.
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UNC9994
0 ImagesUNC9994, an analog of Aripiprazole, is a functionally selective β-arrestin-biased dopamine D2 receptor (D2R) agonist with EC50 <10 nM for β-arrestin-2 recruitment to D2 receptors. UNC9994 is simultaneously partial agonists of β-arrestin-2 translocation and antagonists of Gi-regulated cAMP production. Antipsychotic Activity.
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Ropinirole
0 Images別名: SKF 101468Ropinirole (SKF 101468) is an orally active, potent D3/D2 receptor agonist with a Ki of 29 nM for D2 receptor. Ropinirole has pEC50s of 7.4, 8.4 and 6.8 for hD2, hD3 and hD4 receptors, respectively. Ropinirole has no affinity for the D1 receptors. Ropinirole has the potential for Parkinson's disease.
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Brilaroxazine
0 Images別名: RP5063Brilaroxazine (RP5603) is a potent and orally active multimodal dopamine (DA)/serotonin (5-HT) modulator. Brilaroxazine is a partial agonist of dopamine (DA) D2, D3, and D4 receptors, 5-HT1A (Ki=1.5 nM) and 5-HT2A (Ki=2.5 nM), and has antagonist activity at 5-HT2B (Ki=0.19 nM), and 5-HT7 (Ki=2.7 nM) receptors. Brilaroxazine is an atypical antipsychotic agent, and has the potential to improve cognitive impairments in neuropsychiatric and neurological diseases in vivo.
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Dopamine D4 receptor antagonist-1
0 ImagesDopamine D4 receptor antagonist-1 is a selective DRD4 antagonists, with a Ki of 9.0 nM for Hd4.2. Dopamine D4 receptor antagonist-1 can be used in study of schizophrenia.
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Sonepiprazole
0 Images別名: PNU-101387G; U-101387GSonepiprazole (PNU-101387G) is a selective D4 dopamine antagonist with Kis of 3.6, 10.1, 5147, and 7430 nM for rD4-Dopamine, hD4.2-Dopamine, rD2-Dopamine, and Histamine-H1 receptors, respectively.
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PD 168568 dihydrochloride
0 ImagesPD 168568 dihydrochloride is a orally active and potent dopamine receptor D4 (DRD4) antagonist. PD 168568 dihydrochloride 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 dihydrochloride can be used for glioblastoma (GBM) research.
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L 741742
0 ImagesL 741742 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 suppresses PDGFRβ, ERK1/2, and mTOR signaling pathways, and impairs autophagic flux while disrupting lysosomal function.L 741742 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 can be used for the research of schizophrenia and glioblastoma.
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NGD94-1
0 ImagesNGD94-1 is a potent and selective dopamine D4 receptor antagonist. NGD94-1 shows high affinity for the cloned human D4.2 receptor (Ki = 3.6 nM). NGD94-1 modulates the cognitive functions of the frontostriatal system and regulates dopaminergic transmission in Phencyclidine (PCP)-induced monkeys. NGD94-1 can be used for neurological disease research[1][2].
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Aripiprazole monohydrate
0 Images別名: OPC-14597 monohydrateAripiprazole (OPC-14597) monohydrate, an atypical antipsychotic, is a potent and high-affinity dopamine D2 receptor partial agonist. Aripiprazole monohydrate is an inverse agonist at 5-HT2B and 5-HT2A receptors and displays partial agonist actions at 5-HT1A, 5-HT2C, D3, and D4 receptors. Aripiprazole monohydrate can be used for the research of schizophrenia and COVID19.
