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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Adoprazine
0 ImagesSynonyms: SLV313Adoprazine (SLV313) is a full 5-HT1A receptor agonist with a pEC50 of 9 at cloned h5-HT1A receptors. Adoprazine (SLV313) is a full D2 and D3 receptor antagonist with pA2s of 9.3 and 8.9 at hD2 and hD3 receptors, respectively. Adoprazine (SLV313) has the characteristics of atypical antipsychotics.
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CP 226269
0 ImagesCP 226269 is a potent dopamine D4 receptor agonist that induces calcium flux with EC50 of 32 nM. CP 226269 stimulates phospholipid methylation (PLM) in SK-N-MC neuroblastoma cells with an EC50 of 2.9 nM. CP 226269 can be used in the research of schizophrenia and other related diseases.
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Ro 10-5824 dihydrochloride
0 ImagesRo 10-5824 dihydrochloride is a selective dopamine D4 receptor partial agonist, with Ki of 5.2 nM.
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Pramipexole-d5 dihydrochloride
0 ImagesCat. No.: HY-17355S1CAS No.: 1217601-58-5Pramipexole-d5 dihydrochloride is deuterium labeled Pramipexole dihydrochloride. Pramipexole dihydrochloride 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 can be used for the research of Parkinson's disease (PD) and restless legs syndrome (RLS).
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Ecopipam hydrobromide
0 ImagesSynonyms: SCH 39166 hydrobromideEcopipam (SCH 39166) hydrobromide 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 hydrobromide 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 hydrobromide can be used for the research of schizophrenia and obesity.
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MLS6357
0 ImagesMLS6357 is a D3 dopamine receptor (D3R)-selective positive allosteric modulator (PAM)-antagonist. MLS6357 exhibits antagonist activity in the D3R-mediated and the BRET-based β-arrestin recruitment assay with IC50s of 13 and 14 μM, and no activity for other DAR subtypes (D1R/D2R/D4R/D5R) (IC50 > 100 μM). MLS6357 is also an antagonist in the D3R-mediated Go-BRET assay with an IC50 of 17 μM. MLS6357 can be used for the study of neuropsychiatric disorders, including substance use disorder.
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FAUC 213
0 ImagesFAUC 213 is an orally active and highly selective dopamine D4 receptor complete antagonist with a Ki of 2.2 nM for hD4.4. FAUC 213 has less activity on D2 and D3 receptors (Kis of 3.4 μM, 5.3 μM for hD2, hD3, respectively). FAUC 213 can cross the blood-brain barrier (BBB). FAUC 213 exhibits atypical antipsychotic characteristic.
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A-381393
0 ImagesA-381393 is a potent, selective, brain penetrate dopamine D4 receptor antagonist, with Kis of 1.5, 1.9 and 1.6 nM for human dopamine D4.4, D4.2, and D4.7 receptor, respectively, >2700-fold selectivity over D1, D2, D3 and D5 dopamine receptors. A-381393 shows moderate affinity for 5-HT2A (Ki, 370 nM).
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Fananserin
0 ImagesSynonyms: RP 62203Fananserin (RP 62203) is an orally bioavailable, potent and selective 5-hydroxytryptamine2 (5-HT2) receptor antagonist, with a Ki of 0.37 nM for the rat 5-HT2A receptor. Fananserin also is a selective dopamine D4 receptor antagonist, with a Ki of 2.93 nM for the human dopamine D4 receptor.
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Benzquinamide hydrochloride
0 ImagesSynonyms: P2647 hydrochloride; BZQ hydrochloride; Benzoquinamide hydrochlorideBenzquinamide (P2647; BZQ; Benzoquinamide) hydrochloride is an orally active binder of dopamine receptors and adrenergic receptors. Benzquinamide hydrochloride specifically targets dopamine D2, D3, D4 receptors and α-2A, α-2B, α-2C adrenergic receptors. Benzquinamide hydrochloride 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 hydrochloride has good safety and does not deplete serotonin or norepinephrine in the brain. Benzquinamide hydrochloride can be used in studies related to nausea/vomiting, mental disorders, anxiety states, neurosis, and psychosis.
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ABT-724 trihydrochloride
0 ImagesABT-724 trihydrochloride is a potent and highly selective dopamine D4 receptor agonist with an EC50 of 12.4 nM for human dopamine D4 receptor. ABT-724 trihydrochloride is a potent partial agonist at the rat D4 (EC50 of 14.3 nM) and the ferret D4 receptor (EC50 of 23.2 nM), and has no effect on dopamine D1, D2, D3, or D5 receptors. ABT-724 trihydrochloride could be useful for the treatment of erectile dysfunction and has favorable side-effect profile.
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(-)-Isocorypalmine
0 ImagesSynonyms: Tetrahydrocolumbamine; (S)-Tetrahydrocolumbamine(-)-Isocorypalmine (Tetrahydrocolumbamine; (S)-Tetrahydrocolumbamine) is a dopamine receptor ligand and modulator capable of crossing the blood-brain barrier. (-)-Isocorypalmine exhibits receptor selectivity, acting as a partial agonist of dopamine D1 and D5 receptors (coupled via Gs proteins), as well as an antagonist of D2, D3 and D4 receptors (by blocking Gi protein-mediated signaling). (-)-Isocorypalmine shows no significant binding to various non-dopamine receptors, ion channels and transporters. (-)-Isocorypalmine is metabolically stable in vivo, effectively inhibits spontaneous and cocaine-induced hyperlocomotion, sensitization and conditioned place preference in mice, and does not induce addictive place preference when administered alone. (-)-Isocorypalmine can be used in addiction research.
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(Rac)-Rotigotine hydrochloride
0 ImagesSynonyms: N-0437 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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Blonanserin dihydrochloride
0 ImagesCat. No.: HY-13575ACAS No.: 132812-45-4Synonyms: AD-5423 dihydrochlorideBlonanserin dihydrochloride is a potent and orally active 5-HT2A and dopamine D2 receptor antagonist, with Ki values of 0.812 and 0.142 nM, respectively. Blonanserin dihydrochloride is usually acts as an atypical antipsychotic agent, and can be used for the research of extrapyramidal symptoms, excessive sedation, or hypotension.
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PD 172760
0 ImagesCat. No.: HY-106995CAS No.: 200195-01-3Synonyms: CI 1030PD 172760 (CI 1030) is a selective D4 receptor antagonist. PD 172760 along with the action of other neurotransmitter receptors may be important in study psychosis.
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YM-50001
0 ImagesCat. No.: HY-14331CAS No.: 169451-33-6YM-50001 is a potent and selective dopamine D4 receptor antagonist with a Ki 5.62 nM. YM-50001 can be used for the research of neurological disease .
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NGD 94-1 dimaleate
0 ImagesCat. No.: HY-103405ACAS No.: 179333-18-7NGD 94-1 (dimaleate) is a potent and selective dopamine D4 receptor antagonist. NGD 94-1 (dimaleate) shows high affinity for the cloned human D4.2 receptor (Ki = 3.6 nM). NGD 94-1 (dimaleate) modulates the cognitive functions of the frontostriatal system and regulates dopaminergic transmission in Phencyclidine (PCP)-induced monkeys. NGD 94-1 (dimaleate) can be used for neurological disease research[1][2].
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Pramipexole-d7 dihydrochloride
0 ImagesCat. No.: HY-17355SPramipexole-d7 dihydrochloride is the deuterium labeled Pramipexole dihydrochloride. Pramipexole dihydrochloride 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 can be used for the research of Parkinson's disease (PD) and restless legs syndrome (RLS).
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D4R antagonist-2
0 ImagesCat. No.: HY-163703D4R antagonist-2 (compound 33) is a D4R antagonist. D4R antagonist-2 has a IC50 value of 210 nM, and a Ki value of 59 nM for D4R. D4R antagonist-2 can be used in the Parkinson's disease research.
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PNU-96415E
0 ImagesCat. No.: HY-103404CAS No.: 170856-41-4PNU-96415E is a selective D4/5-HT2A antagonist. PNU-96415E may have potential antipsychotic efficacy.
