What is the mechanism of Racecadotril?

Racecadotril is an anti-diarrheal medication that is particularly effective in treating acute diarrhea. Its mechanism of action is unique and involves the inhibition of enkephalinase, an enzyme located on the brush border of the small intestine. By inhibiting this enzyme, racecadotril prevents the degradation of endogenous enkephalins, small peptides that have a significant role in regulating intestinal secretion.

Enkephalins act on delta-opioid receptors in the gut to reduce the secretion of water and electrolytes into the intestinal lumen. Under normal circumstances, enkephalins are rapidly broken down by enkephalinase, resulting in a short-lived effect. When racecadotril is administered, it inhibits enkephalinase, thereby prolonging the action of enkephalins. This leads to a decreased secretion of fluids and electrolytes, effectively reducing the volume of stool and the frequency of diarrhea.

The action of racecadotril is predominantly antisecretory, rather than affecting intestinal motility. This is a crucial advantage over other anti-diarrheal agents like loperamide, which slow down intestinal transit and can sometimes lead to complications such as toxic megacolon, especially in cases of infectious diarrhea. Because racecadotril does not alter the natural motility of the intestines, it allows for the expulsion of infectious agents and toxins, making it safer for use in various types of diarrhea, including those caused by bacterial infections.

Pharmacokinetically, racecadotril is rapidly absorbed after oral administration and is converted into its active metabolite, thiorphan. Thiorphan is responsible for the inhibition of enkephalinase and the subsequent therapeutic effects. The onset of action is usually within 30 minutes to 2 hours, providing relatively quick relief. The drug is metabolized primarily in the liver and excreted through the kidneys.

Clinical studies have shown racecadotril to be effective in both adults and children suffering from acute diarrhea. It has a favorable safety profile, with minimal side effects, the most common being headache and nausea. Unlike some opioid-based treatments, racecadotril does not cross the blood-brain barrier, thus it does not have central nervous system effects such as sedation or the potential for abuse.

In summary, the mechanism of racecadotril involves the inhibition of enkephalinase, leading to prolonged action of enkephalins, which decrease the secretion of water and electrolytes in the intestines. This antisecretory effect helps to reduce the severity and duration of diarrhea without affecting intestinal motility. Its efficacy and safety profile make it a valuable option in the treatment of acute diarrhea across different age groups.