5-HT2C Receptor (pKi = 9.0)

SB 242084 二盐酸盐（100 nM；45 分钟）在 SH-SY5Y 细胞中表现出对 5-HT 刺激的人 5-HT2C 受体磷脂酰肌醇水解增加的拮抗作用 [1]。 SB 242084 二盐酸盐（1-100 nM；24 小时）可增加 RPTC 呼吸和 PGC-1α mRNA 表达 [2]。细胞活力测定[1] 细胞系：SH-SY5Y 细胞 浓度：100 nM 孵育时间：45 分钟 结果：拮抗 5-HT 诱导的浓度相关的 PI 水解增加。 RT-PCR[2] 细胞系：RPTC 细胞 浓度：1-100 nM 孵育时间：24 小时 结果：FCCP 解偶联呼吸和 PGC-1α mRNA 表达增加。

SB 242084 二盐酸盐（0.1-1 mg/kg；腹腔注射；单次；测试前 20 分钟）可改善大鼠在社交互动测试中的行为[1]。 SB 242084 二盐酸盐（5 mg/kg；腹腔注射；单次；测试前 20 分钟）可改善 mCPP 诱导的大鼠吞咽不足[1]。 SB 242084 diHClide（5、10 mg/kg；腹腔注射；单次）可增加大鼠伏核中基础透析液多巴胺 (DA) 和二羟基苯乙酸 (DOPAC) 的水平[3]。 SB 242084 二盐酸盐（160-640 µg/kg；静脉注射；单次）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放电率，并且体内同一区域的爆发活性也增强。 3]。动物模型：雄性Sprague-Dawley (CD)大鼠[1]。剂量：0.1-1 mg/kg 给药方式：腹腔注射；单身的; 20 分钟预测试结果：在明亮的光线条件下和在不熟悉的测试盒中，老鼠花在社交互动上的时间超过 15 分钟，显着增加。动物模型：雄性Sprague-Dawley（CD）大鼠（mCPP诱导的吞咽功能减退模型）[1]。剂量：5 mg/kg 给药方式：腹腔注射；单身的; 20 分钟预测试结果：从食物呈现之日起 1 小时的测试期内，23 小时食物匮乏的大鼠消耗的食物量显着减少。动物模型：大鼠[2]。剂量：5、10 mg/kg 给药方式：腹腔注射；单一结果：伏隔核中基础透析液多巴胺 (DA) 和二羟基苯乙酸 (DOPAC) 显着增加。

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SB 242084能有效抑制间氯苯哌嗪（mCPP，7 mg/kg i.p.20分钟前测试）诱导的大鼠运动减少，这是一种体内中枢5-HT2C受体功能模型，ID50为0.11 mg/kg i.p.和2.0 mg/kg p.o.SB 242088（0.1-1 mg/kg i.p.）在大鼠社交互动测试中表现出抗焦虑样特征，增加了社交互动的时间，但对运动没有影响。SB 242084（0.1-1mg/kg腹腔注射）也显著增加了大鼠Geller-Seafter焦虑冲突测试中的惩罚反应，但对未惩罚反应没有一致的影响。在大鼠最大电击发作阈值试验中，大剂量的SB 242084（30mg/kg口服）对发作易感性没有影响。此外，虽然SB 242084（试验前1小时口服2和6 mg/kg）拮抗了对mCPP的低剂量反应，但无论是急性还是亚慢性给药，每天两次口服2或6 mg/kg，持续5天，都不会影响食物摄入或体重增加。结果表明，SB 242084是首次报道的选择性强效脑渗透性5-HT2C受体拮抗剂，具有抗焦虑样活性，但不具有缺乏5-HT2C受体的突变小鼠所特有的促惊厥或高吞噬特性。[1]

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]。

本研究的目的是确定5-HT2受体在肾脏线粒体基因和氧化代谢调节中的作用。5-HT2C受体激动剂CP-809101[2-[（3-氯苯基）甲氧基]-6-（1-哌嗪基）吡嗪]和拮抗剂SB-242084[6-氯-2,3-二氢-5-甲基-N-[6-[（2-甲基-3-吡啶基）氧基]-3-吡啶基]-1H-吲哚-1-羧酰胺二盐酸盐]用于检测在存在和不存在5-HT2C受体的情况下，RPTC和小鼠肾脏中肾线粒体基因的诱导和氧化代谢。出乎意料的是，在1-10nM的浓度下，CP-809101和SB-242084都增加了RPTC呼吸和RPTC中过氧化物酶体增殖物激活受体γ辅活化因子-1α（PGC-1α）mRNA的表达。此外，CP-809101和SB-242084增加了小鼠PGC-1α和线粒体蛋白NADH脱氢酶亚基1和NADH脱氢酶（泛醌）β亚复合物8的mRNA表达。这些化合物增加了RPTC（其中5-HT2C受体被小干扰RNA下调）和缺乏5-HT2C受体的小鼠肾皮质中的线粒体基因。相比之下，这些化合物增加PGC-1αmRNA和呼吸的能力在用5-HT2A受体小干扰RNA或5-HT2A受体拮抗剂依普利伐色林处理的RPTC中被阻断。此外，5-HT2A受体激动剂NBOH-2C-CN[4-[2-[[（2-羟基苯基）甲基]氨基]乙基]-2,5-二甲氧基苄腈]在1-100 nM时增加了RPTC呼吸[2]。

SB242084 was daily dissolved in saline containing 8.0% hydroxypropyl-β-cyclodextrin. All drugs were injected i.p. at a volume of 1ml/kg. SB242084 treatment Twenty-nine animals were separated in HR and LR and used for this experiment. After pre-conditioning, animals in both HR and LR groups received the following treatment during the conditioning phase: SB242084 (0.5 mg/kg, i.p.)-cocaine or vehicle (saline containing 8.0% hydroxypropyl-β-cyclodextrin, 1ml/kg, i.p.)-cocaine (n=6–9 per group). Pretreatments were administered 30 minutes before cocaine (20 mg/kg, i.p.) (Burmeister et al. 2004; Fletcher et al. 2002, 2006, 2008; Nic Dhonnchadha et al. 2009). Effects of MDL100907 or SB242084 on CPP acquisition in absence of cocaine Forty animals were separated according to their locomotor activity and used to test the potential conditioning effects induced by MDL100907 and SB242084 when administered alone, and to control for changes in place preference that might spontaneously occur over time. After pre-conditioning, HR and LR animals were divided into three treatment groups: MDL100907 (0.3 mg/kg, i.p.)-Saline, SB242084 (0.5 mg/kg, i.p.)-Saline and Vehicle (saline containing 8.0% hydroxypropyl-β-cyclodextrin, 1ml/kg, i.p.)-Saline (n=5 per group). A fourth treatment group, vehicle (saline containing 8.0% hydroxypropyl-β-cyclodextrin, 1ml/kg, i.p.) followed by cocaine (20 mg/kg, i.p.) was also run in parallel as an internal control for the experiment (n=5 per group). In all cases, pretreatment was followed by treatment 30 minutes later.Reference: Psychopharmacology (Berl). 2012 Apr; 220(4): 731–740. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314106/

[1]. Neuropharmacology . 1997 Apr-May;36(4-5):609-20.

[2]. Psychopharmacology (Berl) . 2006 Mar;185(1):45-57.

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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Rationale: To examine the functional relationship between 5-HT1B receptors (5-HT1B-R) and 5-HT2C receptors (5-HT2C-R) in the control of food intake. Objectives: To compare the hypophagic effect of the 5-HT(2C/1B)-R agonist m-chlorophenylpiperazine (mCPP), with that of the selective 5-HT1B-R agonist CP-94,253 in both wildtype (WT) and 5-HT2C knockout (KO) mice. Methods: The hypophagic effects of mCPP (1, 3 and 5.6 mg/kg) and CP-94,253 (5, 10 and 20 mg/kg) were assessed in WT and 5-HT2C KO mice using the behavioural satiety sequence paradigm. The effects of pre-treatment with the selective 5-HT2C-R antagonist SB 242,084 (0.5 and 1.5 mg/kg) were assessed in two groups of WT mice, with each group given only mCPP or CP-94,253. Results: The 5-HT(2C/1B) receptor agonist mCPP and the selective 5-HT1B receptor agonist CP-94,253 both suppressed food intake in WT mice. 5-HT2C KO mice were insensitive to the hypophagic effects of mCPP but were more sensitive to CP-94,253-induced hypophagia than WT controls. mCPP induced a significant increase in post-prandial activity in 5-HT2C KO mice, but this effect was absent in 5-HT2C KO mice who were given CP-94,253. Data from WT mice, who were pre-treated with the 5-HT2C receptor antagonist SB 242,084 and then challenged with either mCPP or CP-94,253, were similar to those obtained from 5-HT2C KO mice. Conclusions: 5-HT2C-R and 5-HT1B-R activation are each sufficient to induce a hypophagic response. However, concurrent 5-HT2C-R inactivation can potentiate the hypophagic response to 5-HT1B-R activation, consistent with an inhibitory role for the 5-HT2C-R in behaviour mediated by the activation of other 5-HT receptors. These results also confirm that 5-HT1B-R activation alone cannot account for the hyperactive response of 5-HT2C KO mice to mCPP.[2]

C21H21CL3N4O2

467.7760

466.07

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

1049747-87-6

SB 242084; 181632-25-7

16219981

Off-white to light yellow 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

3

4

3

30

551

0

ClC1C(C([H])([H])[H])=C([H])C2=C(C=1[H])N(C(N([H])C1=C([H])N=C(C([H])=C1[H])OC1C([H])=C([H])C([H])=NC=1C([H])([H])[H])=O)C([H])([H])C2([H])[H].Cl[H].Cl[H]

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

SB-242084 HCl; SB 242084; SB242084; 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; SB-242084

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。

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

DMSO : ~100 mg/mL (~213.78 mM)

配方 1 中的溶解度: ≥ 5 mg/mL (10.69 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 50.0 mg/mL澄清DMSO储备液加入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: ≥ 5 mg/mL (10.69 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in 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 50.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 5 mg/mL (10.69 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 50.0 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;
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7、 以上所有助溶剂都可在 Invivochem.cn网站购买。