| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
Renzapride targets multiple serotonin (5-Hydroxytryptamine, 5-HT) receptors, specifically the 5-HT4, 5-HT2b, and 5-HT3 receptors. Its primary therapeutic mechanism is mediated by 5-HT4 receptor agonism, which enhances acetylcholine release in the gastrointestinal tract, promoting GI motility, accelerating gastric emptying, and facilitating colonic transit. Its 5-HT3 antagonism reduces nausea and vomiting, potentially improving tolerability compared to pure 5-HT4 agonists.
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| ln Vitro |
Renzapride is a 5-HT4 receptor agonist with a Ki value of 115 nM. It also acts as an antagonist for the 5HT2b and 5HT3 receptors. The (S)-Renzapride isomer is the form used in pharmacological studies. In vitro, Renzapride promotes smooth muscle contraction in isolated guinea pig ileum or colon via 5-HT4 receptors. This effect is blocked by specific 5-HT4 antagonists like GR 113808, confirming its mechanism of action.
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| ln Vivo |
Renzapride was evaluated in clinical trials for gastrointestinal disorders. In animal models, such as the ferret or rodent, Renzapride accelerates colonic transit and gastric emptying. It was developed as an oral treatment for constipation-predominant irritable bowel syndrome (C-IBS), where it was shown to increase bowel movement frequency and relieve abdominal discomfort in clinical studies. The (S)-enantiomer is the active isomer responsible for these effects in vivo.
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| Enzyme Assay |
Binding affinities are determined using standard radioligand binding assays. For example, membranes from HEK-293 cells expressing the human 5-HT4 receptor are incubated with the radioligand [3H]-GR113808. Non-specific binding is determined in the presence of excess unlabeled 5-HT. Varying concentrations of Renzapride or the (S)-isomer are added, and after incubation, bound ligand is separated by filtration. The Ki is calculated from the IC50 via the Cheng-Prusoff equation.
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| Cell Assay |
Functional activity is measured using cAMP accumulation assays. Cells expressing the 5-HT4 receptor are seeded in 96-well plates. The 5-HT4 receptor is Gs-coupled, so its activation stimulates adenylyl cyclase, increasing intracellular cAMP. Cells are pre-incubated with forskolin (to elevate baseline cAMP) and varying concentrations of test compound. The cAMP concentration is then measured using a competitive ELISA or HTRF kit. The EC50 for stimulation is calculated.
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| Animal Protocol |
In vivo pharmacology studies for 5-HT4 agonists typically utilize rodent models of GI motility. For example, male Sprague-Dawley rats are fasted and then orally administered a charcoal meal or a non-absorbable fluorescent marker. Test compounds (e.g., Renzapride, (S)-isomer) are administered orally or intraperitoneally 30-60 minutes prior. After a set time, the animals are sacrificed, and the distance the marker traveled in the small intestine is measured to calculate the GI transit ratio.
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| ADME/Pharmacokinetics |
Renzapride is an orally active small molecule. The compound has a relatively short half-life in vivo, requiring multiple daily dosing in clinical settings. It is soluble in DMSO and can be formulated for oral gavage in preclinical studies. The (S)-Renzapride isomer is the predominant or active form present in the racemic mixture. Pharmacokinetic parameters are based on the racemate and are characteristic of a rapidly absorbed prokinetic agent.
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| Toxicity/Toxicokinetics |
Toxicity data for (S)-Renzapride is limited to the parent compound Renzapride. Renzapride has been tested in clinical trials and generally had a favorable safety profile. The most common adverse events were mild to moderate diarrhea (associated with the prokinetic effect) and headache. Unlike cisapride, another 5-HT4 agonist, Renzapride was not associated with significant cardiac QT prolongation (hERG channel liability) at therapeutic doses.
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| References |
[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. |
| Additional Infomation |
Renzapride (BRL 24924) was an investigational drug candidate that reached Phase III clinical trials for constipation-predominant Irritable Bowel Syndrome (C-IBS) but was ultimately not approved by the FDA. The (S)-Renzapride isomer is a research-grade compound used for studying the pharmacology of 5-HT4 and 5-HT3 receptors. It remains a valuable pharmacological tool for scientists studying gastrointestinal motility and serotonin signaling pathways.
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| Molecular Formula |
C16H22CLN3O2
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| Molecular Weight |
323.82
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| Appearance |
Typically exists as solid at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~35 mg/mL (~108.08 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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