Prucalopride
A better 5-HT4 prokinetic agent for constipation
Prucalopride is a constipation medication that has passed several clinical trials with flying colors and is expected to become another weapon in the battle against chronic constipation for patients. In 2009 it has come close to approval in European markets under the name retail name Resolori. The company Movetis is responsible for carrying out its clinical trials.
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Prucalopride belongs to a class of compounds known as prokinetic constipation medication, which derive their name from their ability to bind a cellular receptor known as 5-HT4 and induce release of acetylcholine that stimulates muscle movement. Prior, prokinetic agents like tegaserod and cispraside were initially successful in clinical trials. However, after going on the market, reports of cardiac problems led to the drugs' eventual withdrawal.
Non-specificity was the downfall
Some scientists and physicians investigating chronic constipation believe that the early prokinetic agents were not specific enough in binding to their intended target, the 5-HT4 cellular receptor. In other words, the drug was exhibiting off-target effects by binding to other cellular receptors unintentionally which lead to side effects such as cardiac problems. The thought is that prucalopride is a much more specific medication that only hits 5-HT4. There were no clear links to the same cardiovascular problems that arose in earlier prokinetic agents, but the study was too small to conclusively show this.
Successful in the most recent large clinical trial
The phase 3 trial, although too small to conclusively show cardiovascular safety, involved 620 patients who had a history of chronic constipation. The patients were also selected to have hard stools, and the feeling of incomplete emptying of the rectum or straining during bowel movements. Half of the patients received a placebo and the other half prucalopride. For 12 weeks, the patients took medication daily. Physicians recorded how many bowel movements took place every week for the individuals. At the end, it was found that about 29% of the patients who had received prucalopride constipation medication had 3 or more bowel movements per week, whereas the placebo group had only 12% of patients who had the same or better outcome. The other patients who also took prucalopride also increased their average bowel movement frequency. Overall, the conclusion is that the patients taking prucalopride showed significant and substantial improvement in chronic constipation.
Side effects of prucalopride
As with all constipation medications, there were side effects such as headache and abdominal pain. As of 2009, prucalopride is still waiting to be approved. The company Movetis is planning to give the drug a trade name of "Reselor". Movetis does not have many products on the market, and approval of Resolor would likely give it significant market share of the one billion dollars spent on constipation treatments.
Sources:
Medpagetoday.com article on constipation.
Eoff and Lembo, Optimal Treatment of Chronic Constipation in Managed Care, Journal of Managed Care Pharmacy, 2008; 14(9a):Supplement