| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
5-HT4 Receptor 115 nM (Ki)
Renzapride targets serotonin 5-HT4 and 5-HT3 receptors. It is a full agonist of the 5-HT4 receptor and a partial antagonist of the 5-HT3 receptor. It shows high affinity for human 5-HT3 (Ki = 17 nM) and guinea pig 5-HT4 (Ki = 477 nM) receptors. It also acts as a 5-HT2b receptor antagonist. By activating 5-HT4 receptors and blocking 5-HT3 receptors, the compound modulates gastrointestinal motility and secretion. |
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| ln Vitro |
The selective 5-HT receptor antagonist [H3] GR 113808, which has a Ki value of 115 nM, is replaced by renzapride when it comes to binding to cloned human 5-HT4 receptors[3].
In vitro, Renzapride acts as a full 5-HT4 receptor agonist and a 5-HT3 receptor antagonist. Its activity is typically assessed by measuring its ability to stimulate cAMP accumulation (for 5-HT4 agonist activity) or inhibit 5-HT-induced ion flux (for 5-HT3 antagonist activity) in cells expressing the respective receptors. The compound shows Ki values of 17 nM for human 5-HT3 and 477 nM for guinea pig 5-HT4 receptors. It is used in in vitro receptor studies to investigate serotonergic signaling in gastrointestinal tissues. |
| ln Vivo |
Both the delayed solid and liquid meal emptying are partially reversed by renzapride (BRL 24924) (100 µg iv)[2]. Renzapride (BRL 24924), at doses of 0.5–1 mg/kg, dramatically speeds up the rate at which a liquid meal labeled 51Cr exits the mouse stomach[4].
In vivo, Renzapride has been investigated for the treatment of constipation-predominant irritable bowel syndrome (C-IBS). As a 5-HT4 receptor agonist and 5-HT3 receptor antagonist, it would be expected to enhance gastrointestinal motility and reduce visceral hypersensitivity. The compound has been studied in in vivo gastrointestinal motility models. However, comprehensive in vivo efficacy data from published literature are limited. The compound is primarily used as a research tool. |
| Enzyme Assay |
For non-cell-based receptor binding assays, Renzapride can be evaluated using membrane preparations from cells expressing human 5-HT3 or 5-HT4 receptors. Radioligand binding displacement experiments are performed using suitable radiolabeled ligands such as [3H]-GR65630 for 5-HT3 or [3H]-GR113808 for 5-HT4. Membrane homogenates are incubated with increasing concentrations of the test compound and a fixed concentration of the radioligand at room temperature for 60-90 minutes. Bound radioligand is separated from free by rapid filtration through glass fiber filters. Non-specific binding is determined in the presence of excess unlabeled ligand. Ki values are calculated from displacement curves using nonlinear regression analysis.
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| Cell Assay |
For in vitro cellular assays, cells expressing human 5-HT3 or 5-HT4 receptors are cultured in appropriate media. For 5-HT3 antagonist assays, calcium influx is measured using fluorescent calcium indicators. Cells are loaded with the dye and pre-incubated with various concentrations of Renzapride. Receptor activation is stimulated by the addition of a 5-HT3 receptor agonist such as 5-HT. For 5-HT4 agonist assays, cAMP accumulation is measured. Cells are treated with various concentrations of the compound, and cAMP levels are measured using ELISA or HTRF-based detection. EC50 or IC50 values are calculated from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: Dog (simulating gastroparesis)[2]
Doses: 100 µg/kg Route of Administration: iv Experimental Results: Results in a partial reverse of both the delayed solid and liquid meals emptying. Animal/Disease Models: Mice (30-45g)[2] Doses: 0.5-1 mg/kg Route of Administration: po Experimental Results: Dramatically increase the rate of emptying of a 51Cr-labeled liquid meal from the murine stomach. For in vivo animal studies, Renzapride can be administered to rodents via oral gavage or intraperitoneal injection. In models of gastrointestinal motility, gastric emptying, intestinal transit, and colonic motility are assessed following compound administration. In models of irritable bowel syndrome, visceral hypersensitivity and pain responses are evaluated. Dosing regimens vary depending on the specific model and desired exposure levels. Blood and tissue samples may be collected for pharmacokinetic analysis. |
| ADME/Pharmacokinetics |
Renzapride has a molecular weight of 323.82 and a molecular formula of C16H22ClN3O2. It is a mixed 5-HT4 agonist and 5-HT3 receptor antagonist. The compound is supplied as a research-grade compound. It should be stored at -20°C for long-term stability. It is soluble in DMSO and can be formulated for both in vitro and in vivo administration. It is for research use only and is not intended for human consumption.
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| Toxicity/Toxicokinetics |
The toxicity profile of Renzapride has not been extensively reported. As a 5-HT4 receptor agonist and 5-HT3 receptor antagonist, potential adverse effects may include modulation of gastrointestinal motility, which could affect bowel function and transit time. The compound is for research use only and is not intended for human consumption. Standard toxicological evaluation would include acute and repeated-dose toxicity studies, as well as assessment of effects on the gastrointestinal system.
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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. [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. |
| Additional Infomation |
Renzapride is currently in Phase III clinical development in the United States for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). Studies have shown that Renzapride is also effective in treating IBS-C with alternating bowel patterns. This drug was developed by Alizyme in the UK. Drug Indications: For the treatment of constipation-predominant irritable bowel syndrome (IBS-C). Mechanism of Action: Renzapride is a full agonist of the 5-HT4 receptor and a partial antagonist of the 5-HT3 receptor. Pharmacodynamics: Renzapride is a benzamide-substituted drug that acts on the upper gastrointestinal tract. Studies have shown that it promotes gastric emptying in normal subjects; doses of 2 mg and 5 mg reduced the amount of gastric contents aspirated 80 minutes after a meal by 21% and 37%, respectively. Studies have found that Renzapride can dose-dependently shorten oroccipital transit time (assessed by the lactulose/exhaled hydrogen method) in a dose range of 0.2 mg to 5 mg; the 5 mg dose can shorten transit time by 62%.
Renzapride (BRL 24924, CAS 112727-80-7) is a substituted benzamide that functions as a full 5-HT4 receptor agonist and a 5-HT3 receptor antagonist. It is a mixed 5-HT4 agonist and 5-HT3 receptor antagonist. It shows high affinity for human 5-HT3 (Ki = 17 nM) and guinea pig 5-HT4 (Ki = 477 nM) receptors. It has been investigated for the treatment of constipation-predominant irritable bowel syndrome (C-IBS). It is available for research purposes only. |
| Molecular Formula |
C16H22CLN3O2
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|---|---|
| Molecular Weight |
323.82
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| Exact Mass |
323.14
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| CAS # |
112727-80-7
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| PubChem CID |
119574
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| Appearance |
White to off-white solid powder
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| Density |
1.3g/cm3
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| Boiling Point |
469.2ºC at 760mmHg
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| Flash Point |
237.6ºC
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| Vapour Pressure |
5.6E-09mmHg at 25°C
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| Index of Refraction |
1.614
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| LogP |
3.054
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
409
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| Defined Atom Stereocenter Count |
2
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| SMILES |
COC1=CC(N)=C(Cl)C=C1C(N[C@@H]2CCN3CCC[C@H]2C3)=O
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| InChi Key |
GZSKEXSLDPEFPT-IINYFYTJSA-N
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| InChi Code |
InChI=1S/C16H22ClN3O2/c1-22-15-8-13(18)12(17)7-11(15)16(21)19-14-4-6-20-5-2-3-10(14)9-20/h7-8,10,14H,2-6,9,18H2,1H3,(H,19,21)/t10-,14+/m0/s1
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| Chemical Name |
4-amino-N-[(4R,5S)-1-azabicyclo[3.3.1]nonan-4-yl]-5-chloro-2-methoxybenzamide
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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: 25 mg/mL (77.20 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (7.72 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| 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.
Link: https://clinicaltrials.gov/ct2/show/NCT00607971
Conditions:Constipation-Predominant Irritable Bowel SyndromeLink: https://clinicaltrials.gov/ct2/show/NCT00268879
Conditions:Irritable Bowel SyndromeProducts are for research use only; We do not sell to patients
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