| Size | Price | Stock | Qty |
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| 500mg |
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Purity: ≥98%
Racecadotril (also called acetorphan) is a potent and peripherally acting enkephalinase inhibitor used as an antidiarrheal medication. It has an IC50 of 4.5 μM against enkephalinase and prevents the degradation of endogenous enkephalins. Racecadotril has an antisecretory effect; unlike other opioid medications used to treat diarrhea, it lessens the secretion of water and electrolytes into the intestine while also reducing intestinal motility.
| Targets |
Opioid receptor
Neutral endopeptidase (NEP, EC 3.4.24.11), Ki=4 nM (human recombinant NEP) [1] IC50=7 nM (rat intestinal tissue NEP) [2] |
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| ln Vitro |
In the recombinant human NEP enzyme activity assay, the active metabolite thiorphan of Racecadotril (acetorphan) concentration-dependently inhibited NEP activity with a Ki=4 nM, and the inhibition rate reached 92% at 10 nM [1]
In the rat intestinal tissue homogenate assay, the IC50 of Racecadotril (acetorphan) for NEP was 7 nM, and it could completely block NEP-mediated vasoactive intestinal peptide (VIP) degradation at 1 μM [2] In the in vitro intestinal epithelial cell monolayer assay, 100 nM Racecadotril (acetorphan) inhibited PGE2-induced chloride secretion, with the secretion volume decreased by 58% compared to the model group, without affecting the integrity of cell tight junctions [1] |
| ln Vivo |
Racecadotril is quickly converted to Thiorphan in mice after intravenous injection; as a result, 30 minutes after the injection, only Thiorphan is found in the kidney and not the parent compound, Racecadotril[1].
In rats, radioactively labeled racecadotril at a single dose of 10 mg/kg is eliminated in 24 hours in 92% of cases[1]. Racecadotril is an inhibitor of neutral endopeptidase (NEP) that has been shown to have antidiarrheal properties in animals. Racecadotril (100 mg/kg) given orally exhibits effectiveness in a rat model of diarrhea brought on by castor oil[2]. In the rat castor oil-induced acute secretory diarrhea model, oral administration of Racecadotril (acetorphan) dose-dependently inhibited diarrhea. At 10 mg/kg, the diarrhea incidence decreased by 65%, the fecal water content decreased from 89% to 62%, and the number of defecations decreased by 47% [2] In this model, the antidiarrheal effect of 30 mg/kg oral dose was equivalent to 1 mg/kg loperamide, but the onset of action was faster (1 hour vs 2 hours post-administration) [2] In the rat PGE2-induced diarrhea model, oral administration of 5 mg/kg Racecadotril (acetorphan) reduced fecal water content by 53% and intestinal fluid secretion by 41%, while increasing the concentrations of VIP and calcitonin gene-related peptide (CGRP) in intestinal tissue (by 38% and 45%, respectively) [1] In the mouse diarrhea model, oral administration of 20 mg/kg Racecadotril (acetorphan) shortened the duration of diarrhea from 12 hours to 5 hours, without observing constipation side effects [1] |
| Enzyme Assay |
Recombinant NEP enzyme inhibition assay: Gradient concentrations of Racecadotril (acetorphan) were co-incubated with recombinant human NEP and fluorescent substrate. After incubation at 37°C for 30 minutes, the amount of fluorescent product was detected. The Ki value was calculated by nonlinear regression analysis to evaluate the inhibitory affinity of the drug for NEP [1]
Intestinal tissue NEP activity assay: Rat intestinal tissue homogenate was prepared, and the supernatant (containing endogenous NEP) was obtained by centrifugation. Different concentrations of Racecadotril (acetorphan) and radiolabeled VIP substrate were added. After incubation, the undegraded substrate was separated, and NEP activity was quantified by radioactivity counting to calculate the IC50 value [2] |
| Cell Assay |
Intestinal epithelial cell secretion assay: Colonic epithelial cells were seeded in Transwell chambers and cultured until a complete monolayer was formed (stable transepithelial electrical resistance). After pre-incubation with 10-1000 nM Racecadotril (acetorphan) for 1 hour, PGE2 was added to stimulate secretion. The inhibitory effect of the drug on secretory function was evaluated by detecting changes in transepithelial chloride current [1]
Cell tight junction integrity assay: After the above cell experiment, the fluorescein isothiocyanate permeability assay was used to detect the barrier function of the cell monolayer, and the transmembrane permeability of fluorescein isothiocyanate was calculated to verify whether the drug affected epithelial cell integrity [1] |
| Animal Protocol |
6-to-7-week-old male Wistar rats
100 mg/kg A single oral treatment; 30 minutes before castor oil administration. Rat castor oil-induced diarrhea model: Male Wistar rats were acclimated and fasted for 12 hours, then randomly grouped. The experimental group received oral administration of 2.5, 5, 10, 30 mg/kg Racecadotril (acetorphan), with the drug dissolved in normal saline containing 5% polyethylene glycol at an administration volume of 10 mL/kg. The control group received the same volume of vehicle. Thirty minutes after administration, castor oil (10 mL/kg) was intragastrically administered, and the diarrhea incidence, number of defecations, and fecal water content were observed within 4 hours [2] Rat PGE2-induced diarrhea model: Male SD rats were fasted for 12 hours, then the experimental group received oral 5 mg/kg Racecadotril (acetorphan) (dissolved as above). Thirty minutes later, PGE2 (10 μg/kg) was intraperitoneally injected, and diarrhea symptoms were observed within 6 hours. After the experiment, the rats were sacrificed, and the proximal small intestinal tissue was collected to detect VIP and CGRP concentrations [1] Mouse diarrhea model: Female ICR mice were fasted for 8 hours, orally administered 20 mg/kg Racecadotril (acetorphan), and 30 minutes later, senna leaf extract (0.2 g/mL) was intragastrically administered. The onset time, duration of diarrhea, and defecation volume were recorded [1] |
| ADME/Pharmacokinetics |
After oral administration, recadotril (acetyltofen) is rapidly absorbed. In humans, after a single oral dose of 100 mg, the time to peak concentration (Tmax) is 1.5 hours and the peak plasma concentration (Cmax) is 0.8 μg/mL [1]. The oral bioavailability is approximately 30%. The drug is rapidly hydrolyzed in the intestinal mucosa and liver to the active metabolite thiomorphine, which has a time to peak concentration (Tmax) of 2 hours and a peak plasma concentration (Cmax) of 0.3 μg/mL [1]. The elimination half-life (t1/2) of thiomorphine is 2.5 hours, the plasma clearance is 15 mL/min/kg, and the volume of distribution (Vd) is 0.5 L/kg [1]. The drug is mainly excreted by the kidneys, with approximately 65% of the metabolites excreted in the urine and 15% in the feces within 24 hours after administration [1]. The drug can cross the placental barrier, but the fetal plasma concentration is only 12% of the maternal plasma concentration; a small amount of the drug is secreted into breast milk, and the breast milk concentration is about 8% of the maternal plasma concentration [1].
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| Toxicity/Toxicokinetics |
In acute toxicity studies in rats, the oral LD50 of lecardotriol (acetylmorphine) was > 2000 mg/kg, and the intraperitoneal LD50 was > 1000 mg/kg [1]. In long-term toxicity studies in dogs, oral administration of 300 mg/kg daily for 6 months did not cause significant toxic symptoms, and no abnormalities were found in liver and kidney function, hematological indicators, or histopathological examination [1]. Human plasma protein binding rate: Thiomorphine is approximately 90%, mainly bound to albumin [1]. No significant drug interactions were found. No enhanced efficacy or cumulative toxicity was observed when used in combination with loperamide, antibiotics, or antihistamines [1]. There were no significant differences in pharmacokinetic parameters between children and the elderly, and no dose adjustment was required [1].
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| References |
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| Additional Infomation |
2-[[2-[(acetylthio)methyl]-1-oxo-3-phenylpropyl]amino]acetic acid (phenylmethyl) ester is an N-acyl amino acid. Recadotril has been used in basic scientific research and treatment of diarrhea, acute diarrhea, and acute gastroenteritis. Recadotril (acetylmorphine) is a prodrug. After oral administration, it is converted to the active metabolite thiomorphine by esterases in the intestine and liver. It exerts its antidiarrheal effect by specifically inhibiting neutrophil elastase (NEP), reducing the degradation of antisecretory peptides (such as vasoactive intestinal peptide and calcitonin gene-related peptide) in the intestine, and regulating intestinal water and sodium balance [1][2]. The clinical indication is acute diarrhea, applicable to adults and children (including newborns). It can shorten the course of diarrhea, reduce the amount and frequency of bowel movements, and does not affect normal intestinal peristalsis, with no risk of constipation [1]. Compared with loperamide, recadotril (acetyltofen) is more effective for secretory diarrhea, especially for infectious diarrhea (such as rotavirus infection), and does not affect the excretion of intestinal pathogens [1][2]. Clinically recommended dose: 100 mg for adults, 3 times a day; 5 mg/kg for children, divided into 3 doses, for a course of treatment not exceeding 7 days [1].
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| Molecular Formula |
C21H23NO4S
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| Molecular Weight |
385.48
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| Exact Mass |
385.134
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| Elemental Analysis |
C, 65.43; H, 6.01; N, 3.63; O, 16.60; S, 8.32
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| CAS # |
81110-73-8
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| Related CAS # |
Racecadotril-d5; 1246815-11-1
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| PubChem CID |
107751
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
574.5±50.0 °C at 760 mmHg
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| Melting Point |
89ºC
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| Flash Point |
301.2±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.579
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| LogP |
3.44
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
27
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| Complexity |
485
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CNC(C(CC1C=CC=CC=1)CSC(C)=O)=O)OCC1C=CC=CC=1
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| InChi Key |
ODUOJXZPIYUATO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H23NO4S/c1-16(23)27-15-19(12-17-8-4-2-5-9-17)21(25)22-13-20(24)26-14-18-10-6-3-7-11-18/h2-11,19H,12-15H2,1H3,(H,22,25)
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| Chemical Name |
benzyl 2-[[2-(acetylsulfanylmethyl)-3-phenylpropanoyl]amino]acetate
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.49 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 (6.49 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 (6.49 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 | 2.5942 mL | 12.9708 mL | 25.9417 mL | |
| 5 mM | 0.5188 mL | 2.5942 mL | 5.1883 mL | |
| 10 mM | 0.2594 mL | 1.2971 mL | 2.5942 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05600062 | Recruiting | Drug: Placebo Drug: Racecadotril 100 milligram (MG) Oral Capsule |
Acute Respiratory Distress Syndrome |
Queen Mary University of London |
August 24, 2023 | Not Applicable |
| NCT01577043 | Completed | Drug: Racecadotril Drug: Placebo |
Acute Diarrhea Acute Gastroenteritis |
Centro Pediatrico Albina de Patino |
September 2011 | Phase 4 |
| NCT05216822 | Completed | Drug: Racecadotril | Acute Watery Diarrhea | Assiut University | June 1, 2018 | Phase 1 |
| NCT01153854 | Completed | Drug: Racecadotril Drug: Placebo groups |
Diarrhea | National Institute of Pediatrics, Mexico |
January 2007 | Phase 3 |
| NCT03473561 | Completed | Drug: Racecadotril plus ORS | Diarrhea, Infantile | Abbott | August 25, 2018 | Phase 3 |
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