D2 Receptor
Dopamine D2 receptor (D2R) provides negative-feedback control of dopamine neuron firing, dopamine synthesis, reuptake, and release, making it a core regulator of dopaminergic transmission[1]. Mechanistically, D2R signaling connects Gi activation, β-arrestin recruitment, receptor trafficking, and striatal A2A-D2R-AC5 complexes that integrate adenosine and dopamine signals in striatopallidal neurons[2][3][4]. In disease models, altered D2R signaling appears in schizophrenia-related assays, DYT1 dystonia, Huntington’s disease models, Parkinson’s disease research, and substance-use-disorder biology[1][2][5][6][7]. Compared with related isoforms, D2R-short, but not D2R-long, couples to the RhoA/ROCK/cofilin pathway and contributes to striatal vulnerability to expanded huntingtin[6]. This isoform distinction is experimentally important because D2R-short also supports dopamine- and TGFβ1-mediated growth inhibition in pituitary lactotropes[8]. For research applications, D2R agonists such as quinpirole, bromocriptine, ropinirole-related ligands, and radiolabeled MCL-536 help define receptor activity, D2high states, and disease-linked signaling responses[7][9][10]. D2R antagonists including haloperidol and clozapine show concentration-dependent dopamine antagonism, while haloperidol displays stronger β-arrestin-2 inhibition than Gi antagonism under specific assay conditions[2].
References:
- [1]. Chen R, et al. Dopamine D2 autoreceptor interactome: Targeting the receptor complex as a strategy for treatment of substance use disorder. Pharmacol Ther. 2020 Sep;213:107583. [Content Brief]
- [2]. Silva RR, et al. Evaluation of Functional Selectivity of Haloperidol, Clozapine, and LASSBio-579, an Experimental Compound With Antipsychotic-Like Actions in Rodents, at G Protein and Arrestin Signaling Downstream of the Dopamine D2 Receptor. Front Pharmacol. 2019 Jun 4;10:628. [Content Brief]
- [3]. Tirotta E, et al. Signaling by dopamine regulates D2 receptors trafficking at the membrane. Cell Cycle. 2008 Jul 15;7(14):2241-8. [Content Brief]
- [4]. Ferré S, et al. Essential Control of the Function of the Striatopallidal Neuron by Pre-coupled Complexes of Adenosine A2A -Dopamine D2 Receptor Heterotetramers and Adenylyl Cyclase. Front Pharmacol. 2018 Apr 9;9:243. [Content Brief]
- [5]. Scarduzio M, et al. Strength of cholinergic tone dictates the polarity of dopamine D2 receptor modulation of striatal cholinergic interneuron excitability in DYT1 dystonia. Exp Neurol. 2017 Sep;295:162-175. [Content Brief]
- [6]. Galan-Rodriguez B, et al. Coupling of D2R Short but not D2R Long receptor isoform to the Rho/ROCK signaling pathway renders striatal neurons vulnerable to mutant huntingtin. Eur J Neurosci. 2017 Jan;45(1):198-206. [Content Brief]
- [7]. Subburaju S, et al. The High Affinity Dopamine D2 Receptor Agonist MCL-536: A New Tool for Studying Dopaminergic Contribution to Neurological Disorders. ACS Chem Neurosci. 2021 Apr 21;12(8):1428-1437. [Content Brief]
- [8]. Sarkar DK, et al. Dopamine, dopamine D2 receptor short isoform, transforming growth factor (TGF)-beta1, and TGF-beta type II receptor interact to inhibit the growth of pituitary lactotropes. Endocrinology. 2005 Oct;146(10):4179-88. [Content Brief]
- [9]. Subburaju S, et al. New Dopamine D2 Receptor Agonist, [3H]MCL-536, for Detecting Dopamine D2high Receptors in Vivo. ACS Chem Neurosci. 2018 Jun 20;9(6):1283-1289. [Content Brief]
- [10]. Mickevicius NJ. Locally Linearized Approximation of RF Pulse Propagators for Faster Simulation of Magnetization Dynamics With Slice Profile Effects in 2D MR Fingerprinting. Magn Reson Med. 2026 Jun 8. doi: 10.1002/mrm.70462. Epub ahead of print. PMID: 42260330. et al. Locally Linearized Approximation of RF Pulse Propagators for Faster Simulation of Magnetization Dynamics With Slice Profile Effects in 2D MR Fingerprinting. Magn Reson Med. 2026 Jun 8. [Content Brief]
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D2 Receptor Related Products (297)
Related Products (297)
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FLA-797
0 ImagesCat. No.: HY-182381CAS No.: 84226-14-2FLA-797 is a brain-penetrant dopamine D2 receptor blocker and very low affinity for dopamine D1 receptors. FLA-797 selectively binds to and blocks postsynaptic dopamine D2 receptors. FLA-797 induces catalepsy in male rats. FLA-797 blocks dopamine agonist-induced hypothermia in male rats. FLA-797 contributes marginally to the dopamine D2 receptor-blocking activity of Remoxipride (HY-101313) in male rats. FLA-797 does not mimic the atypical antipsychotic profile of Remoxipride. FLA-797 can be used for research on mental disorders.
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Fluphenazine decanoate dihydrochloride
0 ImagesFluphenazine decanoate dihydrochloride is a CNS-penetrant dopamine D2 receptor inhibitor, is a long-acting phenothiazine neuroleptic. Fluphenazine can be used for schizophrenia research.
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SEP-4199
0 ImagesCat. No.: HY-14545BCAS No.: 2974362-88-2SEP4199 is an orally active 5-HT7 receptor ligand, with a Ki value of 66 nM for human 5-HT7R and 16 nM for human D2R. SEP4199 mediates antidepressant effects. SEP4199 is applicable for the research of bipolar depression.
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Risperidone mesylate
0 ImagesCat. No.: HY-11018BCAS No.: 666179-96-0Synonyms: R 64 766 mesylateRisperidone mesylate(R 64 766 mesylate) is a serotonin 5-HT2 receptor blocker, P-Glycoprotein inhibitor and potent dopamine D2 receptor antagonist, with Kis of 4.8, 5.9 nM for 5-HT2A and dopamine D2 receptor, respectively.
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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.
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Blonanserin-d5
0 ImagesCat. No.: HY-13575S1CAS No.: 1346599-86-7Synonyms: AD-5423-d5Blonanserin-d5 (AD-5423-d5) is a deuterium labeled Blonanserin (HY-13575). Blonanserin is a dopamine D2/5-HT2 receptor antagonist and an atypical antipsychotic.
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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.
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Methopromazine maleate
0 ImagesMethopromazine maleate is a dopamine D2 receptor (Dopamine D2 receptor) antagonist belonging to the phenothiazine class of compounds, with an LD50 of 366 mg/kg in mouse studies. Methopromazine maleate competitively binds to and blocks G-protein coupled receptors (GPCR) in the central nervous system, thereby inhibiting downstream signal transduction. Methopromazine maleate can be used in research on chronic schizophrenia.
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Metopimazine-d6
0 ImagesCat. No.: HY-116578SCAS No.: 1215315-86-8Synonyms: EXP999-d6; RP9965-d6Metopimazine-d6 (EXP999-d6; RP9965-d6) is the deuterium labeled Metopimazine (HY-116578). Metopimazine (EXP999; RP9965) is a phenothiazine, orally available, selective dopamine D2 receptor antagonist that does not penetrate the blood-brain barrier. Metopimazine blocks dopamine D2 receptors in the chemoreceptor trigger zone and the periphery, thereby inhibiting nausea and vomiting. Metopimazine is indicated for chemotherapy-induced nausea and vomiting, and has low central side effects due to its poor brain penetration. The use of metopimazine in acute gastroenteritis may have potential risks.
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Melperone (Standard)
0 ImagesMelperone (Standard) is the analytical standard of Melperone (HY-B2169). This product is intended for research and analytical applications. Melperone is a butyrophenone with atypical antipsychotic properties. Melperone is a multireceptor antagonist with Kds of 102 nM, 180 nM, 180 nM, and 150 nM for 5-HT2A, dopamine D2, α1-adrenergic, and α2-adrenergic receptors, respectively. Melperone has weak binding to histamine H1, 5-HT2C, 5-HT1A, 5-HT1D, and muscarinic receptors, with Kd values of 580 nM, 2100 nM, 2200 nM, 3400 nM, >10000 nM, respectively. Melperone is also a CYP2D6 inhibitor. Melperone can be used for the study of schizophrenia, and agitation in the elderly.
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Melperone-d4 hydrochloride
0 ImagesMelperone-d4 hydrochloride is the deuterium labeled Melperone hydrochloride (HY-103109). Melperone hydrochloride is a butyrophenone with atypical antipsychotic properties. Melperone hydrochloride is a multireceptor antagonist with Kds of 102 nM, 180 nM, 180 nM, and 150 nM for 5-HT2A, dopamine D2, α1-adrenergic, and α2-adrenergic receptors, respectively. Melperone hydrochloride has weak binding to histamine H1, 5-HT2C, 5-HT1A, 5-HT1D, and muscarinic receptors, with Kd values of 580 nM, 2100 nM, 2200 nM, 3400 nM, >10000 nM, respectively. Melperone hydrochloride is also a CYP2D6 inhibitor. Melperone hydrochloride can be used for the study of schizophrenia, and agitation in the elderly.
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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.
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Savoxepine
0 ImagesCat. No.: HY-W747310CAS No.: 79262-46-7Synonyms: Cipazoxapine; CGP 19486ASavoxepine (Cipazoxapine; CGP 19486A) is a dopamine antagonist with antipsychotic activity. Savoxepine preferentially blocks hippocampal dopamine D2 receptors and also inhibits dopamine-stimulated adenylate cyclase activity. Savoxepine shows strong interactions with α-adrenergic receptors, serotonin 5-HT2 receptors and histamine H1 receptors, and moderate interactions with α2-adrenergic receptors, histamine H2 receptors, serotonin 5-HT1 receptors and cholinergic muscarinic receptors. Savoxepine inhibits dopamine agonist-induced stereotyped behaviors in animals, induces catalepsy in animals, and antagonizes Apomorphine (HY-12723)-induced climbing behavior in mice. Savoxepine can be used in schizophrenia-related research.
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Haloperidol-d4 N-Oxide
0 ImagesCat. No.: HY-14538S2CAS No.: 1246815-56-4Haloperidol-d4 N-Oxide is the deuterium labeled Haloperidol. Haloperidol is a potent dopamine D2 receptor antagonist, widely used as an antipsychotic.
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Sumanirole
0 ImagesCat. No.: HY-70081CAS No.: 179386-43-7Synonyms: PNU-95666ESumanirole (PNU-95666E) is a highly selective D2 receptor full agonist with an ED50 of about 46 nM. Sumanirole plays an important role in the research of Parkinson's disease and restless leg syndrome.
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ADX-10061
0 ImagesCat. No.: HY-19100CAS No.: 128022-68-4Synonyms: CEE 03-310; NNC 687ADX-10061 (compound NNC 687) is a dopamine D1 receptor antagonist with the Ki values of 9.1 nM, 5.8 nM, > 10 000 nM and 355 nM for adenylyl cyclase, D1, D2 and 5-HT2 receptor, respectively. ADX-10061 can be used for study of schizophrenia.
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Cinuperone
0 ImagesCat. No.: HY-W754019CAS No.: 82117-51-9Cinuperone is a multi-target competitive receptor ligand and σ receptor antagonist that acts on Dopamine D1, σ, Dopamine D1, and 5-HT2 receptors. Cinuperone shows significantly higher affinity for σ receptors than for Dopamine D1 receptors, and only exhibits moderate binding activity for dopamine D2 receptors. Cinuperone can be used in the research of central nervous system diseases.
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BRD5814
0 ImagesCat. No.: HY-123788CAS No.: 1953181-29-7BRD5814 is a D2R antagonist. BRD5814 can be used in schizophrenia research.
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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).
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Biriperone
0 ImagesCat. No.: HY-137935CAS No.: 42021-34-1Synonyms: CentbutindoleBiriperone is a D1, D2, and 5-HT2A receptor antagonist with pKi values of 6.372, 7.88 and 7.619. Biriperone blocks amphetamine-induced hyperactivity and stereotypy in rodents. Biriperone blocks secondary conditioned avoidance responses in rodents. Biriperone can be used for the research of schizophrenia.
