Renzapride
(Synonyms: BRL 24924) 目录号 : GC67923Renzapride (BRL 24924)，是一种取代苯甲酰胺，是 5-HT4 受体激动剂，也是 5HT2b 和 5HT3 受体拮抗剂。Renzapride (BRL 24924) 可以用于便秘型肠易激综合征 (C-IBS) 的研究。
Cas No.:112727-80-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Renzapride (BRL 24924), a substituted benzamide, is a full 5-HT4 receptor agonist with a Ki value of 115 nM. Renzapride (BRL 24924) is also a 5HT2b and 5HT3 receptor antagonist[1]. Renzapride could be used for constipation predominant irritable bowel syndrome (C-IBS) study[2].
Renzapride replaces specific binding of [H3] GR 113808 (a selective 5-HT receptor antagonist) to cloned human 5-HT4 receptors with a Ki value of 115 nM[3].
Renzapride (BRL 24924) (100 µg i.v.) results in a partial reverse of both the delayed solid and liquid meals emptying[2].
Renzapride (BRL 24924) (0.5-1 mg/kg) significantly increases the rate of emptying of a 51Cr-labeled liquid meal from the murine stomach[4].
| Animal Model: | Dog (simulating gastroparesis)[2] |
| Dosage: | 100 µg/kg |
| Administration: | i.v. |
| Result: | Results in a partial reverse of both the delayed solid and liquid meals emptying. |
| Animal Model: | Mice (30-45g)[2] |
| Dosage: | 0.5-1 mg/kg |
| Administration: | p.o. |
| Result: | Significantly increase the rate of emptying of a 51Cr-labeled liquid meal from the murine stomach. |
[1]. Camilleri M, et al. Effect of renzapride on transit in constipation-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol. 2004;2(10):895-904.
[2]. Scarpellini E, et al. Renzapride: a new drug for the treatment of constipation in the irritable bowel syndrome. Expert Opin Investig Drugs. 2008;17(11):1663-1670.
[3]. Nagakura Y, et al. Pharmacological properties of a novel gastrointestinal prokinetic benzamide selective for human 5-HT4 receptor versus human 5-HT3 receptor. Pharmacol Res. 1999;39(5):375-382.
[4]. Mawe GM, et al. Blockade of 5-HT-mediated enteric slow EPSPs by BRL 24924: gastrokinetic effects. Am J Physiol. 1989;257(3 Pt 1):G386-G396.
| Cas No. | 112727-80-7 | SDF | Download SDF |
| 别名 | BRL 24924 | ||
| 分子式 | C16H22ClN3O2 | 分子量 | 323.82 |
| 溶解度 | DMSO : 25 mg/mL (77.20 mM; Need ultrasonic) | 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 | 3.0881 mL | 15.4407 mL | 30.8814 mL |
| 5 mM | 0.6176 mL | 3.0881 mL | 6.1763 mL |
| 10 mM | 0.3088 mL | 1.5441 mL | 3.0881 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。
Renzapride: a new drug for the treatment of constipation in the irritable bowel syndrome
Expert Opin Investig Drugs 2008 Nov;17(11):1663-70.PMID:18922103DOI:10.1517/13543784.17.11.1663.
Renzapride is a novel drug currently under clinical evaluation for the treatment of irritable bowel syndrome (IBS). Renzapride is a mixed 5-hydroxytryptamine type 4 (5-HT4) agonist and 5-HT3 receptor antagonist that has a stimulatory effect on gastrointestinal motility and transit, as established by in vivo and in vitro studies. Its therapeutic efficacy, tolerability and safety have been evaluated in diabetic gastroparesis in a single study, as well as in IBS in a few other studies. Phase II studies indicated potential beneficial effects on symptoms and bowel habits in patients with constipation-predominant IBS and mixed-type IBS. The outcome of Phase III studies is currently under evaluation.
Efficacy and tolerability of Renzapride in irritable bowel syndrome: a meta-analysis of randomized, controlled clinical trials including 2528 patients
Arch Med Sci 2014 Feb 24;10(1):10-8.PMID:24701208DOI:10.5114/aoms.2014.40729.
Introduction: By targeting different subtypes of 5-hydroxytryptamine (5HT) receptors in the gastrointestinal (GI) tract, several drugs have been introduced for the management of irritable bowel syndrome (IBS). Renzapride is a full agonist for 5HT4 receptor and an antagonist to 5HT2b and 5HT3 receptors which is thought a promising therapeutic agent for constipation predominant IBS (C-IBS) patients due to its accelerating effect on the GI tract. In this meta-analysis, our aim was to evaluate the efficacy and tolerability of Renzapride in the management of IBS. Material and methods: A search was done from 1992 to February 2013 for placebo-controlled trials that investigated the efficacy of Renzapride in IBS. Results: Relative risk (RR) for clinical efficacy in IBS patients treated for 5 weeks or less comparing Renzapride to placebo was 1.07 (95% CI = 0.89-1.29, p = 0.38). This value for IBS patients treated for more than 5 weeks was 1.04 (95% CI = 0.78-1.239, p = 0.77). The RR for clinical efficacy in IBS patients treated with Renzapride (4 mg) for 5 weeks or less and more than 5 weeks in comparison to placebo was 1.2 (95% CI = 0.97-1.48, p = 0.1) and 1.16 (95% CI = 0.98-1.37, p = 0.08), respectively, which were statistically non-significant but clinically important. The analysis of tolerability demonstrated that amongst different reported adverse effects, Renzapride caused diarrhea more than placebo (RR = 1.61 with a 95% CI = 1.16-2.24, p = 0.004). The RR for withdrawals from Renzapride compared to placebo was 1.58 (95% CI = 1.26-2.07, p = 0.0007). Conclusions: Renzapride is not superior to placebo in relieving IBS symptoms and causes significant incidences of diarrhea and drop-outs due to adverse effects in treated patients vs. placebo. Thus, this medicine might be a cost burden to patients without providing good effectiveness.
Pharmacology and metabolism of Renzapride : a novel therapeutic agent for the potential treatment of irritable bowel syndrome
Drugs R D 2008;9(1):37-63.PMID:18095752DOI:10.2165/00126839-200809010-00004.
Background and objective: Renzapride (ATL-1251), a novel benzamide, is currently under clinical development for the treatment of irritable bowel syndrome (IBS). Previous in vitro and in vivo experimental studies have characterized Renzapride as a full serotonin 5-HT(4) receptor agonist on the gut and a 5-HT(3) receptor antagonist. Clinical studies have confirmed the therapeutic efficacy, tolerability and safety of Renzapride in patients with constipation-predominant IBS. This study set out to characterize the pharmacological profile of Renzapride and its potential metabolic products at both 5-HT and other monoamine receptors in the gut. Methods: The affinity of Renzapride, its (+) and (-) enantiomers, and its primary metabolite, Renzapride N-oxide and its enantiomers, for serotonin receptors was assessed by means of in vitro radioligand binding inhibition studies. After membranes prepared from animal tissue or membranes of cell lines transfected with cloned human receptors had been incubated with radiolabelled ligand with high affinity for a specific receptor, Renzapride was added to competitively inhibit this binding. Levels of bound radioligand were measured by filtration and counting of the bound radioactivity. In instances where >50% inhibition of radioligand binding had occurred, the inhibition constant (K(i)) was calculated. Metabolism of Renzapride by liver microsomes was assessed by incubating 10 micromol/L Renzapride with human liver microsome samples for 60 minutes at 37 degrees C. After the reaction was stopped, the samples were centrifuged and the supernatant analysed for metabolites by high-pressure liquid chromatography (HPLC). The potential inhibitory effects of Renzapride on cytochrome P450 (CYP) enzymes were assessed by incubating Renzapride at various concentrations over a 1-500 micromol/L concentration range with microsomes genetically engineered to express a single CYP. Results: Renzapride was selective for serotonergic receptors and, in particular, had high affinity for human 5-HT(3) and guinea-pig 5-HT(4) receptors (K(i) 17 and 477 nm, respectively). Inhibitory properties at 5-HT(2B) receptors were also identified for Renzapride, as well as some affinity for 5-HT(2A) and 5-HT(2C) receptors. Renzapride N-oxide and its enantiomers demonstrated much lower affinity for all 5-HT receptors compared with Renzapride. Renzapride was metabolized by liver microsomes to a limited extent and there was no significant non-microsomal metabolism of Renzapride. Renzapride did not inhibit the major CYP drug-metabolizing enzymes CYP2C9, CYP2D6, CYP1A2, CYP2A6, CYP2C19, CYP2E1 or CYP3A4 at concentrations consistent with use in a clinical setting. Conclusions: These results confirm and extend earlier studies in animal and human receptors that show Renzapride is a potent and generally full 5-HT(4) receptor agonist and 5-HT(3) receptor antagonist. The results reported in the present study indicate that the metabolites of Renzapride are minor and are unlikely to contribute to its therapeutic profile or lead to interaction of Renzapride with other drugs that inhibit the major drug-metabolizing enzymes in the liver at therapeutic doses. These data contribute to the understanding of the pharmacological actions and metabolic fate of Renzapride in vivo.
Effect of Renzapride on transit in constipation-predominant irritable bowel syndrome
Clin Gastroenterol Hepatol 2004 Oct;2(10):895-904.PMID:15476153DOI:10.1016/s1542-3565(04)00391-x.
Background & aims: The aim of this study was to evaluate the dose-ranging pharmacodynamic effects of Renzapride, a 5-hydroxytryptamine 4 (5-HT4) receptor full agonist/5-HT3 receptor antagonist, on gastrointestinal transit and symptoms in patients with constipation-predominant irritable bowel syndrome (C-IBS). Methods: Forty-eight patients (46 women) with C-IBS underwent recording of baseline symptoms for 1 week. Twelve patients per group were randomized (double-blind, parallel design) to 11-14 days of Renzapride (1, 2, or 4 mg) or placebo, once daily. Daily bowel habits and weekly satisfactory relief of IBS symptoms were recorded. At the end of treatment, gastric emptying (GE), small bowel transit (SBT), and colon transit (CT) were measured by scintigraphy. The relationship between CT and bowel function was evaluated. Results: A statistically significant linear dose response to Renzapride was detected for CT (GC8 h, P = 0.004; GC24 h, P = 0.056), and ascending colon (AC) emptying t1/2 (P = 0.019), but not for GE (t1/2, P = 0.088; or SBT, P = 0.41). AC half-time transit (t1/2) for placebo and 4 mg of Renzapride were (median) 17.5 vs. 5.0 hours, respectively. Improved bowel function scores (stool form and ease of passage, but not frequency) were significantly (P < 0.05) associated with accelerated CT. Pharmacokinetic analysis showed linear kinetics of Renzapride with a mean t1/2 in plasma of 10 hours. Bowel function and satisfactory relief were not significantly altered by Renzapride, although a type II error cannot be excluded. No significant adverse clinical, laboratory, or electrocardiogram (ECG) effects were observed. Conclusions: Renzapride causes clinically significant dose-related acceleration of CT, particularly ascending colonic emptying; this acceleration of transit is associated with improvement of bowel function in female C-IBS patients.
Pilot study of the efficacy of Renzapride on gastrointestinal motility and symptoms in patients with constipation-predominant irritable bowel syndrome
Aliment Pharmacol Ther 2006 Jun 1;23(11):1655-65.PMID:16696817DOI:10.1111/j.1365-2036.2006.02940.x.
Aim: To investigate the efficacy and safety of Renzapride, a potent 5-hydroxytryptamine type-4 receptor full agonist and 5-hydroxytryptamine type-3 receptor antagonist in patients with constipation-predominant irritable bowel syndrome. Methods: In this dose-escalating pilot study, 17 patients with constipation-predominant irritable bowel syndrome received placebo, Renzapride 2 mg o.d. and Renzapride 2 mg b.d. sequentially for 28 days. Response was determined by radio-opaque marker measurement of overall gastrointestinal and segmental colonic transit and patients' assessment of their irritable bowel syndrome symptoms. Results: Renzapride reduced mean overall gastrointestinal transit time (placebo, 2.9 +/- 1.6 days; Renzapride 2 mg o.d., 2.6 +/- 1.4 days; Renzapride 2 mg b.d., 1.9 +/- 1.6 days) (P = 0.024) and accelerated segmental colonic transit, with statistically significant differences for Renzapride 2 mg b.d. over placebo in caecum/ascending colon (P = 0.019) and descending colon (P = 0.022). Renzapride also reduced abdominal pain, increased the number of pain-free days and improved stool consistency. The frequency of reported adverse events was similar on Renzapride and placebo. Conclusions: Renzapride is well-tolerated, stimulates gastrointestinal transit and improves symptoms in patients with constipation-predominant irritable bowel syndrome, particularly at the 2 mg b.d. dose, where improvements in gastrointestinal symptoms were evident over placebo. This study has established proof of concept and supports further investigation of Renzapride in patients with constipation-predominant irritable bowel syndrome.