Racecadotril
[CAS# 81110-73-8]

Identification

• Classification: API >> Digestive system medication >> Laxative antidiarrheal
• Name: Racecadotril
• Synonyms: N-[2-[(Acetylthio)methyl]-1-oxo-3-phenylpropyl]-glycine phenylmethyl ester; Acetorphan; Tiorfan
• Molecular Formula: C₂₁H₂₃NO₄S
• Molecular Weight: 385.48
• CAS Registry Number: 81110-73-8
• EC Number: 688-010-7
• SMILES: CC(=O)SCC(CC1=CC=CC=C1)C(=O)NCC(=O)OCC2=CC=CC=C2

Properties

• Solubility: 10 mg/mL(DMSO) (Expl.)
• Density: 1.2±0.1 g/cm³, Calc.^*
• Melting point: 89 °C
• Index of Refraction: 1.579, Calc.^*
• Boiling Point: 574.5±50.0 °C (760 mmHg), Calc.^*
• Flash Point: 301.2±30.1 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS09 Warning
• Risk Statements: H302-H400
• Safety Statements: P264-P270-P273-P301+P317-P330-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Skin sensitization	Skin Sens.	1B	H317
Skin irritation	Skin Irrit.	2	H315
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Skin sensitization	Skin Sens.	1	H317

Discovery and Applications

Racecadotril is an antidiarrheal medication commonly used to treat acute diarrhea. It functions by inhibiting enkephalinase, an enzyme that breaks down enkephalins, which are endogenous peptides involved in regulating intestinal function. By inhibiting enkephalinase, racecadotril increases the levels of enkephalins, which in turn reduces excessive fluid secretion in the intestine, a primary cause of diarrhea. This mechanism is different from other antidiarrheal drugs, such as loperamide, which work by slowing down the movement of the intestines.

Racecadotril was first developed in the 1980s and has since been widely used, particularly in Europe and parts of Asia. Unlike other antidiarrheal agents that directly affect gastrointestinal motility, racecadotril's action focuses on the secretion of water and electrolytes into the bowel, making it a safer option for treating diarrhea without the risk of constipation or paralytic ileus.

The drug is typically used for the treatment of acute diarrhea in both children and adults. It is particularly effective in managing diarrhea caused by infections, such as rotavirus, or other gastrointestinal disturbances. Racecadotril has been shown to be effective in reducing the frequency and severity of diarrhea, as well as the duration of symptoms, without significantly affecting gut motility. This makes it particularly beneficial in treating diarrhea associated with viral infections, where fluid loss and dehydration are significant concerns.

One of the main advantages of racecadotril over other antidiarrheal agents is its favorable safety profile. It is generally well tolerated, with few side effects. Some mild side effects such as skin rashes, nausea, and headaches may occur, but these are relatively uncommon. The drug does not have the sedative effects associated with some other antidiarrheals, such as diphenoxylate or loperamide, which can cause drowsiness or discomfort. It is also less likely to lead to the risk of misuse, as it does not possess the same addictive properties as some opioid-based antidiarrheal agents.

Racecadotril is available in oral form, commonly as capsules or powder for oral suspension, making it convenient for both pediatric and adult patients. It is typically taken with or after meals, and the dosage is adjusted based on the patient's age and the severity of the condition.

While racecadotril is generally used for the management of acute diarrhea, it has also been explored for use in other gastrointestinal conditions, such as irritable bowel syndrome (IBS), where its ability to reduce secretion could potentially benefit patients experiencing diarrhea-predominant IBS. However, its use in IBS is not as widespread, and more research is needed to fully assess its efficacy in this context.

In addition to its use in human medicine, racecadotril has also been studied for its potential veterinary applications, particularly in treating diarrhea in dogs and other animals. This aspect of its use, however, is less well-documented compared to its human applications.

As with any medication, it is essential to use racecadotril under medical supervision. While it is effective in managing symptoms, it does not address the underlying causes of diarrhea, such as bacterial or viral infections. Therefore, racecadotril is typically used as part of a broader treatment regimen, which may include rehydration therapy and, when necessary, antibiotics or antivirals.

In summary, racecadotril is an effective, well-tolerated treatment for acute diarrhea, with a unique mechanism of action that focuses on reducing intestinal secretion rather than motility. Its ability to reduce fluid loss without affecting gut function makes it a valuable option for managing diarrhea, particularly in cases caused by infections. Although further studies are needed to explore its use in other gastrointestinal conditions, racecadotril remains a useful tool in managing diarrhea and improving patient outcomes.

References

1986. Pharmacological properties of acetorphan, a parenterally active 'enkephalinase' inhibitor. The Journal of Pharmacology and Experimental Therapeutics, 237(3).
DOI: 10.1016/s0022-3565(25)24995-3

2023. Racecadotril versus loperamide for the treatment of acute diarrhoea. The Egyptian Journal of Internal Medicine, 35(1).
DOI: 10.1186/s43162-023-00217-0

2024. Management of acute infectious gastroenteritis in infants and young children. Paediatrics & Paedology, 59(3).
DOI: 10.1007/s00608-024-01235-z