SCH 23390 hydrochloride
(Synonyms: R-(+)-SCH-23390 hydrochloride) 目录号 : GC10892
SCH 23390 hydrochloride 是一种高效的选择性多巴胺 D1 样受体拮抗剂，对 D1 和 D5 多巴胺受体亚型的 K(i) 分别为 0.2 和 0.3 nM。
Cas No.:125941-87-9
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >99.00%
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- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
BV - 2 cell lines |
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Preparation Method |
SCH 23390 hydrochloride was added to B-2 cell medium. |
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Reaction Conditions |
1uM SCH 23390 hydrochloride hydrochloride |
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Applications |
As DRD1 and DRD2 inhibitor, SCH 23390 hydrochloride hydrochloride is able to reverse the isosibiricin-mediated inhibition of the NLRP3/caspase-1 inflammasome pathway. |
| Animal experiment [2]: | |
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Animal models |
Adult female CD-1 mice |
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Preparation Method |
To examine the potential mechanisms by which high-dose DA induces ductus constriction, isolated vessels were first exposed to newborn oxygen conditions before receiving pretreatment with 10 -6 M of a DA1-like receptor antagonist (SCH 23390 hydrochloride), followed by exposure to increasing concentrations of DA. |
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Dosage form |
Pretreat isolated ductus with 10-6 M SCH 23390 hydrochloride |
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Applications |
SCH 23390 hydrochloride augments dopamine-induced ductus constriction in CD-1 mouse vessels under newborn O2 conditions. |
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References: [1]. Wang YH, Lv HN, et,al. Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway. Acta Pharmacol Sin. 2020 Feb;41(2):173-180. doi: 10.1038/s41401-019-0296-7. Epub 2019 Sep 10. PMID: 31506572; PMCID: PMC7471458. [2]. Crockett SL, Harris M, et,al. Role of dopamine and selective dopamine receptor agonists on mouse ductus arteriosus tone and responsiveness. Pediatr Res. 2020 May;87(6):991-997. doi: 10.1038/s41390-019-0716-x. Epub 2019 Dec 9. PMID: 31816622; PMCID: PMC7196482. |
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SCH 23390 hydrochloride is a highly potent and selective dopamine D1-like receptor antagonist with a K(i) of 0.2 and 0.3 nM for the D1 and D5 dopamine receptor subtypes, respectively. In vitro, it also binds with high affinity to the 5-HT2 and 5-HT1C serotonin receptor subtypes[1].As a potent and high efficacy human 5-HT2C receptor agonist with a Ki of 9.3 nM. SCH-23390 hydrochloride inhibits G protein-coupled inwardly rectifying potassium (GIRK) channels with an IC50 of 268 nM[2,3].
SCH 23390 hydrochloride (1?μM) treatment reverses the inhibitory effects of Isosibiricin on NLRP3 expression and the cleavages of caspase-1 and IL-1β in the LPS-induced BV-2 cells. SCH 23390 hydrochloride could reverse the Isosibiricin-mediated inhibition of the NLRP3/caspase-1 inflammasome pathway[4].Pretreatment of primary astrocytes with the DRD1 antagonistSCH 23390 hydrochloride did not reduce cabergoline induced GSH synthesis[6].
In spontaneously hypertensive rats, fenoldopam produced a dose-dependent reduction in arterial pressure and a significant increase in mesenteric and renal blood flow, and pretreatment with the DA 1-like receptor antagonist SCH 23390 hydrochloride significantly attenuated these effects[5]. C57BL/6J mice were injected with the D1R antagonist SCH 23390 hydrochloride, and a decrease in social behavior was seen, producing autism-like behavior[7]. The effects of Aβ on memory in Per2 mice were investigated, and the increased Aβ levels did not influence the memory performance of Per2 mice after SCH 23390 hydrochloride treatment[9].SCH 23390 hydrochloride and Haloperidolwere administered during CPP. The accompanying changes in phosphorylation of extracellular signal-regulated kinase (ERK) in MLDS related brain regions, including the ventral tegmental area (VTA), caudate putamen (CPu), prefrontal cortex (PFC), and nucleus accumbens (NAc) were measured in the CPP mice. Results revealed that 60% N2O induced CPP in the gas-administered mice and promoted the ERK phosphorylation (p-ERK) in the NAc and CPu during the test session of the CPP test. Pretreatment of SCH 23390 hydrochloride(0.5 mg/kg) inhibited the acquisition of N2O-induced CPP and the enhanced p-ERK in NAc[8].
References:
[1]: Bourne JA. SCH 23390: the first selective dopamine D1-like receptor antagonist. CNS Drug Rev. 2001 Winter;7(4):399-414. doi: 10.1111/j.1527-3458.2001.tb00207.x. PMID: 11830757; PMCID: PMC6741643.
[2]: Millan MJ, Newman-Tancredi A, et,al. The "selective" dopamine D1 receptor antagonist, SCH23390, is a potent and high efficacy agonist at cloned human serotonin2C receptors. Psychopharmacology (Berl). 2001 Jun;156(1):58-62. doi: 10.1007/s002130100742. PMID: 11465634.
[3]: Kuzhikandathil EV, Oxford GS. Classic D1 dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) directly inhibits G protein-coupled inwardly rectifying potassium channels. Mol Pharmacol. 2002 Jul;62(1):119-26. doi: 10.1124/mol.62.1.119. PMID: 12065762.
[4]: Wang YH, Lv HN, et,al. Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway. Acta Pharmacol Sin. 2020 Feb;41(2):173-180. doi: 10.1038/s41401-019-0296-7. Epub 2019 Sep 10. PMID: 31506572; PMCID: PMC7471458.
[5]: Crockett SL, Harris M, et,al. Role of dopamine and selective dopamine receptor agonists on mouse ductus arteriosus tone and responsiveness. Pediatr Res. 2020 May;87(6):991-997. doi: 10.1038/s41390-019-0716-x. Epub 2019 Dec 9. PMID: 31816622; PMCID: PMC7196482.
[6]: Wei Y, Lu M, et,al. Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection. Nat Commun. 2020 Feb 18;11(1):941. doi: 10.1038/s41467-020-14788-x. PMID: 32071304; PMCID: PMC7029000.
[7]: Li Y, Luo ZY, et,al. The gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis in EphB6-deficient mice. Microbiome. 2020 Aug 20;8(1):120. doi: 10.1186/s40168-020-00884-z. PMID: 32819434; PMCID: PMC7441571.
[8]: Yang T, Yue G, et,al. SCH 23390 inhibits the acquisition of nitrous oxide-induced conditioned place preference and the changes in ERK phosphorylation expression in nucleus accumbens of mice. Neurosci Lett. 2022 Jun 11;781:136674. doi: 10.1016/j.neulet.2022.136674. Epub 2022 May 4. PMID: 35525502.
[9]: Kim M, Custodio RJ, et,al. Per2 Expression Regulates the Spatial Working Memory of Mice through DRD1-PKA-CREB Signaling. Mol Neurobiol. 2022 Jul;59(7):4292-4303. doi: 10.1007/s12035-022-02845-z. Epub 2022 May 4. PMID: 35508866.
SCH 23390 hydrochloride 是一种高效的选择性多巴胺 D1 样受体拮抗剂，对 D1 和 D5 多巴胺受体亚型的 K(i) 分别为 0.2 和 0.3 nM。在体外，它还以高亲和力结合 5-HT2 和 5-HT1C 血清素受体亚型[1]。作为一种有效且高效的人 5-HT2C 受体激动剂，Ki 为 9.3 nM . SCH-23390 hydrochloride 抑制 G 蛋白偶联内向整流钾 (GIRK) 通道，IC50 为 268 nM[2,3]。
SCH 23390 盐酸盐 (1μM) 处理可逆转 Isosibiricin 对 LPS 诱导的 BV-2 细胞中 NLRP3 表达和 caspase-1 和 IL-1β 裂解的抑制作用。 SCH 23390 hydrochloride 可以逆转 Isosibiricin 介导的 NLRP3/caspase-1 炎症通路抑制[4]。用 DRD1 拮抗剂 SCH 23390 hydrochloride 预处理原代星形胶质细胞不会减少卡麦角林诱导的 GSH 合成 [6].
在自发性高血压大鼠中，非诺多泮可剂量依赖性地降低动脉压并显着增加肠系膜和肾血流量，用 DA 1 样受体拮抗剂 SCH 23390 盐酸盐预处理可显着减弱这些作用[ 5]。给 C57BL/6J 小鼠注射 D1R 拮抗剂 SCH 23390 盐酸盐，观察到社交行为下降，产生自闭症样行为[7]。研究了 Aβ 对 Per2 小鼠记忆的影响，增加的 Aβ 水平不影响 SCH 23390 盐酸盐处理后 Per2 小鼠的记忆性能[9]。在 CPP 期间给予 SCH 23390 盐酸盐和氟哌啶醇.在 MLDS 相关脑区，包括腹侧被盖区 (VTA)、尾状壳核 (CPu)、前额叶皮层 (PFC) 和伏隔核 (NAc)，细胞外信号调节激酶 (ERK) 磷酸化的伴随变化被测量CPP小鼠。结果显示，60% N2O 在气体给药的小鼠中诱导了 CPP，并在 CPP 测试的测试期间促进了 NAc 和 CPu 中的 ERK 磷酸化（p-ERK）。 SCH 23390盐酸盐(0.5 mg/kg)预处理抑制N2O诱导的CPP的获得和增强的NAc中p-ERK[8]。
| Cas No. | 125941-87-9 | SDF | |
| 别名 | R-(+)-SCH-23390 hydrochloride | ||
| 化学名 | (R)-8-chloro-3-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol hydrochloride | ||
| Canonical SMILES | ClC1=C(C=C2[C@@H](C3=CC=CC=C3)CN(C)CCC2=C1)O.Cl | ||
| 分子式 | C17H18ClNO.HCl | 分子量 | 324.24 |
| 溶解度 | DMF: 15 mg/ml,DMSO: 20 mg/ml,DMSO:PBS (pH 7.2) (1:7): 0.12 mg/ml,Ethanol: 5 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0841 mL | 15.4207 mL | 30.8414 mL |
| 5 mM | 0.6168 mL | 3.0841 mL | 6.1683 mL |
| 10 mM | 0.3084 mL | 1.5421 mL | 3.0841 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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Blockade of dopamine D 1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels
J Psychopharmacol2017 Oct;31(10):1334-1346.PMID: 28950781DOI: 10.1177/0269881117731162
Background: Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D1-family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice.
Methods: Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D1-family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle.
Results: Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly.
Conclusions: Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D1-family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D1-family receptors supports the hypothesis that D1 and/or D5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.