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]
-
D4 Receptor Related Products (92)
Related Products (92)
-
D4R antagonist-1
0 ImagesCat. No.: HY-145905CAS No.: 2846077-19-6D4R antagonist-1 is a potent and selective D4R antagonist with an IC50 of 6.87 µM. D4R antagonist-1 has the potential for the research of Parkinson’s disease.
-
ABT-724
0 ImagesABT-724, a chemical probe, is a potent and highly selective dopamine D4 receptor agonist with an EC50 of 12.4 nM for human dopamine D4 receptor. ABT-724 is a potent partial agonist at the rat D4 (EC50 of 14.3 nM) and the ferret D4 receptor (EC50 of 23.2 nM). ABT-724 has no effect on dopamine D1, D2, D3, or D5 receptors. ABT-724 could be useful for the treatment of erectile dysfunction and has favorable side-effect profile.
-
Alentemol
0 ImagesCat. No.: HY-124524CAS No.: 112891-97-1Synonyms: U-66444B free baseAlentemol (U-66444B (free base)) is a blood-brain barrier-permeable dopamine receptor D1, D2, D3, and D4 agonist. Alentemol inhibits dopamine release, reduces dopamine synthesis, regulates dopamine metabolism, suppresses the impulse activity of dopaminergic neurons, and decreases the impulse frequency of dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area. Alentemol is applicable to research related to schizophrenia.
-
Ropinirole-d4 hydrochloride
0 ImagesCat. No.: HY-B0623ASCAS No.: 1330261-37-4Synonyms: SKF 101468-d4 hydrochlorideRopinirole-d4 (SKF 101468-d4) hydrochloride is the deuterium labeled Ropinirole hydrochloride. Ropinirole hydrochloride is a potent D3/D2 receptor agonist with a Kiof 29 nM for D2 receptor. Ropinirole hydrochloride has pEC50s of 7.4, 8.4 and 6.8 for hD2, hD3 and hD4 receptors, respectively. Ropinirole hydrochloride has no affinity for the D1 receptors. Ropinirole hydrochloride has the potential for Parkinson's disease.
-
Iloperidone hydrochloride
0 ImagesCat. No.: HY-17410ACAS No.: 1299470-39-5Synonyms: HP 873 hydrochlorideIloperidone hydrochloride (HP 873 hydrochloride) is a D2/5-HT2 receptor antagonist. Iloperidone hydrochloride is an atypical antipsychotic for the schizophrenia symptoms.
-
FAUC-312
0 ImagesCat. No.: HY-121740CAS No.: 562104-72-7FAUC-312, a tetrahydropyrimidine, is a strong and highly selective dopamine D4 receptor partial agonist (Ki=1.5 nM).
-
Dopamine D3 receptor ligand-5
0 ImagesCat. No.: HY-156239CAS No.: 2899250-94-1Dopamine D3 receptor ligand-5 (13a), a Cariprazine (HY-14763) analogue, is a dopamine D3 receptor ligand, with Ki values of 2.85 nM and 0.14 nM for D2R and D3R, respectively.
-
Alentemol hydrobromide
0 ImagesCat. No.: HY-115418CAS No.: 112892-81-6Synonyms: U-68553BAlentemol hydrobromide (U-66444B) is a blood-brain barrier-permeable dopamine receptor D1, D2, D3, and D4 agonist. Alentemol hydrobromide inhibits dopamine release, reduces dopamine synthesis, regulates dopamine metabolism, suppresses the impulse activity of dopaminergic neurons, and decreases the impulse frequency of dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area. Alentemol hydrobromide is applicable to research related to schizophrenia.
-
NRA-0160
0 ImagesCat. No.: HY-101641CAS No.: 204718-47-8NRA-0160 is a selective dopamine D4 receptor antagonist, with a Ki value of 0.48 nM and with negligible affinity for dopamine D2 receptor (Ki: >10000 nM), D3 receptor (Ki: 39 nM), rat 5-HT2A receptor (Ki: 180 nM) and rat α1 adrenoceptor (Ki: 237 nM).
-
ABT-670
0 ImagesCat. No.: HY-19483CAS No.: 630119-43-6ABT-670 is a selective, oral bioavailable agonist of dopamine D4 receptor, with EC50 of 89 nM, 160 nM, and 93 nM for human D4, ferret D4, and rat D4, respectively.
-
U-101958 maleate
0 ImagesCat. No.: HY-123663CAS No.: 224170-09-6Synonyms: PNU-101958 maleateU-101958 (PNU-101958) maleate is a highly selective ligand and antagonist for dopamine D4 receptor, with an IC50 of 2.7 nM. U-101958 maleate behaves as an agonist in HEK-293 cells expressing the human recombinant D4.4 receptor. U-101958 maleate is an antipsychotic.
-
Benzquinamide
0 ImagesBenzquinamide (P2647; BZQ; Benzoquinamide) is an orally active binder of dopamine receptors and adrenergic receptors. Benzquinamide specifically targets dopamine D2, D3, D4 receptors and α-2A, α-2B, α-2C adrenergic receptors. Benzquinamide regulates blood pressure and heart rate, attenuates the pressor effect of adrenaline, and exhibits activities such as antiemesis, anxiolysis, and reduction of histamine-induced bronchoconstriction. Benzquinamide has good safety and does not deplete serotonin or norepinephrine in the brain. Benzquinamide can be used in studies related to nausea/vomiting, mental disorders, anxiety states, neurosis, and psychosis.
