5-HT2C Receptor (pKi = 9.0)

据报道，SB 242084（100 nM；45 分钟）对 SH-SY5Y 细胞中人 5-HT2C 工作站中 5-HT 磷脂酰肌醇工作站的增加具有多重拮抗作用 [1]。 SB 242084（1–100 Nm；二十四小时）

在社交互动测试中，SB 242084（0.1–1 mg/kg；腹腔注射；单剂量；20 分钟预测试）可改善行为 [1]。 SB 242084（160-640 μg/kg；IV；单剂量）剂量依赖性地显着增加 VTA（腹侧被盖区）多巴胺能神经元的基础电流率以及体内 (DOPAC) 水平。 SB 242084（5 mg/kg；腹腔注射；单剂量；20 分钟） SB 242084（5、10 mg/kg；腹腔注射；单剂量）可增加伏隔核中的基础透析液多巴胺 (DA) 和六苯形式 [3]。同一区域的突发活动也有所增加 [3]。

SB 242084对克隆的人5-HT2C受体具有高亲和力（pKi 9.0），分别比密切相关的克隆人5-HT2B和5-HT2A亚型具有100倍和158倍的选择性。SB 242084对一系列其他5-HT、多巴胺和肾上腺素能受体具有超过100倍的选择性。在使用稳定表达克隆的人5-HT2C受体的SH-SY5Y细胞对5-HT刺激的磷脂酰肌醇水解的研究中，SB 242084作为拮抗剂，pKb为9.3，与相应的受体结合亲和力非常相似[1]。

细胞活力测定[1]
细胞类型： SH-SY5Y 细胞
测试浓度： 100 nM
孵育时间： > 45 分钟
实验结果： 拮抗 5-HT 诱导的浓度相关增加）增加 RPTC 呼吸和 PGC-1α mRNA 表达 [2]。在PI水解中。

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RT-PCR[2]
细胞类型： RPTC 细胞
测试浓度： 1-100 nM
孵育持续时间：24小时
实验结果：FCCP解耦呼吸并增加PGC-1α mRNA表达。

Animal/Disease Models: Male SD (SD (Sprague-Dawley)) (CD) rat [1].
Doses: 0.1-1 mg/kg
Route of Administration: intraperitoneal (ip) injection; single; 20 minutes Pre-test
Experimental Results: Rats spent Dramatically more time in social interactions over 15 minutes under bright light conditions and in unfamiliar test boxes.

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Animal/Disease Models: Male SD (SD (Sprague-Dawley)) (CD) rats (mCPP-induced Hypophagia model) [1].
Doses: 5 mg/kg
Route of Administration: intraperitoneal (ip) injection; single; 20-minute pre-test
Experimental Results: 23 hrs (hrs (hours)) of food deprivation during a 1-hour test period from the date of food presentation The amount of food consumed by rats was Dramatically diminished.

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Animal/Disease Models: Rat [2].
Doses: 5, 10 mg/kg
Route of Administration: intraperitoneal (ip) injection; Single
Experimental Results:Basal dialysate dopamine (DA) and diamine in the nucleus accumbens Hydroxyphenylacetic acid (DOPAC) was Dramatically increased.

[1]. SB 242084, a selective and brain penetrant 5-HT2C receptor antagonist. Neuropharmacology. 1997 Apr-May;36(4-5):609-20.

[2]. 5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists. J Pharmacol Exp Ther. 2016 Apr;357(1):1-9.

6-chloro-5-methyl-N-[6-(2-methylpyridin-3-yl)oxypyridin-3-yl]-2,3-dihydroindole-1-carboxamide;dihydrochloride is an organic molecular entity, an indole alkaloid and a pyridine. It has a role as a receptor modulator.

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SB 242084 has a high affinity (pKi 9.0) for the cloned human 5-HT2C receptor and 100- and 158-fold selectivity over the closely related cloned human 5-HT2B and 5-HT2A subtypes respectively. SB 242084 had over 100-fold selectivity over a range of other 5-HT, dopamine and adrenergic receptors. In studies of 5-HT-stimulated phosphatidylinositol hydrolysis using SH-SY5Y cells stably expressing the cloned human 5-HT2C receptor, SB 242084 acted as an antagonist with a pKb of 9.3, which closely resembled its corresponding receptor binding affinity. SB 242084 potently inhibited m-chlorophenylpiperazine (mCPP, 7 mgkg i.p. 20 min pre-test)-induced hypolocomotion in rats, a model of in vivo central 5-HT2C receptor function, with an ID50 of 0.11 mg/kg i.p., and 2.0 mg/kg p.o. SB 242084 (0.1-1 mg/kg i.p.) exhibited an anxiolytic-like profile in the rat social interaction test, increasing time spent in social interaction, but having no effect on locomotion. SB 242084 (0.1-1 mg/kg i.p.) also markedly increased punished responding in a rat Geller-Seifter conflict test of anxiety, but had no consistent effect on unpunished responding. A large acute dose of SB 242084 (30 mg/kg p.o.) had no effect on seizure susceptibility in the rat maximal electroshock seizure threshold test. Also, while SB 242084 (2 and 6 mg/kg p.o. 1 hr pre-test) antagonized the hypophagic response to mCPP, neither acute nor subchronic administration of the drug, for 5 days at 2 or 6 mg/kg p.o. twice daily, affected food intake or weight gain. The results suggest that SB 242084 is the first reported selective potent and brain penetrant 5-HT2C receptor antagonist and has anxiolytic-like activity, but does not possess either proconvulsant or hyperphagic properties which are characteristic of mutant mice lacking the 5-HT2C receptor.[1]

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In acute organ injuries, mitochondria are often dysfunctional, and recent research has revealed that recovery of mitochondrial and renal functions is accelerated by induction of mitochondrial biogenesis (MB). We previously reported that the nonselective 5-HT2 receptor agonist DOI [1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine] induced MB in renal proximal tubular cells (RPTCs). The goal of this study was to determine the role of 5-HT2 receptors in the regulation of mitochondrial genes and oxidative metabolism in the kidney. The 5-HT2C receptor agonist CP-809,101 [2-[(3-chlorophenyl)methoxy]-6-(1-piperazinyl)pyrazine] and antagonist SB-242,084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] were used to examine the induction of renal mitochondrial genes and oxidative metabolism in RPTCs and in mouse kidneys in the presence and absence of the 5-HT2C receptor. Unexpectedly, both CP-809,101 and SB-242,084 increased RPTC respiration and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA expression in RPTCs at 1-10 nM. In addition, CP-809,101 and SB-242,084 increased mRNA expression of PGC-1α and the mitochondrial proteins NADH dehydrogenase subunit 1 and NADH dehydrogenase (ubiquinone) β subcomplex 8 in mice. These compounds increased mitochondrial genes in RPTCs in which the 5-HT2C receptor was downregulated with small interfering RNA and in the renal cortex of mice lacking the 5-HT2C receptor. By contrast, the ability of these compounds to increase PGC-1α mRNA and respiration was blocked in RPTCs treated with 5-HT2A receptor small interfering RNA or the 5-HT2A receptor antagonist eplivanserin. In addition, the 5-HT2A receptor agonist NBOH-2C-CN [4-[2-[[(2-hydroxyphenyl)methyl]amino]ethyl]-2,5-dimethoxybenzonitrile] increased RPTC respiration at 1-100 nM. These results suggest that agonism of the 5-HT2A receptor induces MB and that the classic 5-HT2C receptor agonist CP-809,101 and antagonist SB-242,084 increase mitochondrial genes and oxidative metabolism through the 5-HT2A receptor. To our knowledge, this is the first report that links 5-HT2A receptor agonism to mitochondrial function.[2]

C21H19N4O2CL.2[HCL]

467.77604

466.073

C, 53.92; H, 4.53; Cl, 22.74; N, 11.98; O, 6.84

181632-25-7

SB 242084 dihydrochloride;1049747-87-6

3644637

Off-white to pink solid powder

1.4±0.1 g/cm3

620.1±55.0 °C at 760 mmHg

328.8±31.5 °C

0.0±1.8 mmHg at 25°C

1.671

3.76

67.35

1

4

3

28

551

0

GCMNSEILNIPNSX-UHFFFAOYSA-N

InChI=1S/C21H19ClN4O2.2ClH/c1-13-10-15-7-9-26(18(15)11-17(13)22)21(27)25-16-5-6-20(24-12-16)28-19-4-3-8-23-14(19)2;;/h3-6,8,10-12H,7,9H2,1-2H3,(H,25,27);2*1H

6-chloro-5-methyl-N-[6-(2-methylpyridin-3-yl)oxypyridin-3-yl]-2,3-dihydroindole-1-carboxamide;dihydrochloride

6-Chloro-5-methyl-N-(6-((2-methylpyridin-3-yl)oxy)pyridin-3-yl)indoline-1-carboxamide dihydrochloride; SB 242084 hydrochloride; SB 242084 (hydrochloride); SB-242084 Dihydrochloride; SB 242084 dihydrochloride; SB 242084 dihydrochloride hydrate;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 44 mg/mL (~111.43 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.33 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (6.33 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。