RS 127445是一种具有口服活性的高选择性5-羟色胺受体2B（5-HT2B）受体拮抗剂，pKi为9.5，对5-HT2B的选择性是对5-HT2A、5-HT2C等其他相关受体的1000倍以上。
Cas No.:199864-87-4
Sample solution is provided at 25 µL, 10mM.
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RS 127445 is an orally active, highly selective 5-HT2B receptor antagonist with a pKi of 9.5 and a selectivity for 5-HT2B that is more than 1000 times greater than that for other related receptors such as 5-HT2A and 5-HT2C[1, 2]. 5-HT2B receptors play important roles in the central and peripheral nervous systems, participating in the regulation of various physiological functions, such as cardiovascular effects and neuronal sensitization[3]. RS 127445 can inhibit dopamine neurotransmission in the nucleus accumbens[4].
In vivo, intraperitoneal injection of RS 127445 (1-30mg/kg) in mice significantly inhibited intestinal peristalsis and reduced fecal output in a dose-dependent manner[5]. RS 127445 (10mg/kg) significantly inhibited visceral hypersensitivity induced by restraint stress in experimental visceral hypersensitivity rats when administered orally, with an inhibition rate of 74%, and also reduced defecation[6].
References:
[1] Bonhaus D W, Flippin L A, Greenhouse R J, et al. RS‐127445: a selective, high affinity, orally bioavailable 5‐HT2B receptor antagonist[J]. British journal of pharmacology, 1999, 127(5): 1075-1082.
[2] Maroteaux L. Gene structure, expression, and 5-HT2B receptor signaling[M]//5-HT2B Receptors: From Molecular Biology to Clinical Applications. Cham: Springer International Publishing, 2021: 1-32.
[3] Monassier L. 5-HT2B Receptor, the Heart and Blood Vessels[M]//5-HT2B Receptors: From Molecular Biology to Clinical Applications. Cham: Springer International Publishing, 2021: 153-163.
[4] Cathala A, Devroye C, Robert É, et al. Serotonin2B receptor blockade in the rat dorsal raphe nucleus suppresses cocaine-induced hyperlocomotion through an opposite control of mesocortical and mesoaccumbens dopamine pathways[J]. Neuropharmacology, 2020, 180: 108309.
[5] Bassil A K, Taylor C M, Bolton V J N, et al. Inhibition of colonic motility and defecation by RS‐127445 suggests an involvement of the 5‐HT2B receptor in rodent large bowel physiology[J]. British journal of pharmacology, 2009, 158(1): 252-258.
[6] Ohashi‐Doi K, Himaki D, Nagao K, et al. A selective, high affinity 5‐HT2B receptor antagonist inhibits visceral hypersensitivity in rats[J]. Neurogastroenterology & Motility, 2010, 22(2): e69-e76.
RS 127445是一种具有口服活性的高选择性5-羟色胺受体2B（5-HT2B）受体拮抗剂，pKi为9.5，对5-HT2B的选择性是对5-HT2A、5-HT2C等其他相关受体的1000倍以上[1, 2]。5-HT2B受体在中枢神经系统和外周神经系统中发挥重要作用，参与调节多种生理功能，如心血管效应和神经元敏化[3]。RS 127445能够抑制伏隔核（nucleus accumbens）中的多巴胺（dopamine）神经传递[4]。
在体内，RS 127445（1-30mg/kg）通过腹腔注射处理小鼠，显著抑制了小鼠的肠蠕动，呈剂量依赖性地减少了小鼠的粪便排出量[5]。RS 127445（10mg/kg）通过口服治疗实验性内脏超敏大鼠，显著抑制了束缚应激诱发的内脏超敏反应，抑制率为74%，还减少了排便[6]。
| Animal experiment [1]: | |
Animal models | Adult male C57BL/6J mice |
Preparation Method | Animals were given the test compound (RS 127445 1, 3, 10 or 30mg/kg) or vehicle (10% ethanol, 40% polyethylene glycol, 50% distilled H2O) intraperitoneally in a final dose volume of 3mL/kg. Following drug administration, animals were returned to the home cage. Three hours following treatment, the faecal output was collected and weighed; pellets were collected onto paper tray liners, to minimize contamination from urine or water. Because of a high variability in the numbers and sizes of faecal pellets excreted by individual rats, the results are expressed as the mean wet weight SEM of pellets excreted. |
Dosage form | 1, 3, 10 or 30mg/kg; i.p. |
Applications | RS 127445 (1-30 mg/kg), dose-dependently reduced faecal output, reaching significance at 10 and 30mg/kg. |
References: | |
| Cas No. | 199864-87-4 | SDF | |
| 别名 | 2-氨基-4-(4-氟萘-1-基)-6-异丙基嘧啶,RS-127445; MT 500; RS127445 | ||
| 化学名 | 4-(4-fluoronaphthalen-1-yl)-6-isopropylpyrimidin-2-amine | ||
| Canonical SMILES | FC1=CC=C(C2=CC(C(C)C)=NC(N)=N2)C3=CC=CC=C31 | ||
| 分子式 | C17H16FN3 | 分子量 | 281.33 |
| 溶解度 | ≥ 15.89mg/mL in DMSO | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5545 mL | 17.7727 mL | 35.5454 mL |
| 5 mM | 710.9 μL | 3.5545 mL | 7.1091 mL |
| 10 mM | 355.5 μL | 1.7773 mL | 3.5545 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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