Phase II drugs under clinical investigation for the treatment of chronic constipation

by Selleckchem | Sep 10 2023

Introduction: Chronic constipation (CC) is a common gastrointestinal (GI) motility disorder that significantly impairs the quality of life in affected subjects. As almost half of the patients suffering from CC are not satisfied with currently available medicines, there is a need to develop new molecules with better effectiveness and tolerability.

Areas covered: The authors include all experimental and clinical trials (up to Phase II) about new investigational drugs for the treatment of CC. The article identifies nine new agents: mitemcinal, TD-8954, YKP10811, itopride, RM-131, KWA-0711, elobixibat, velusetrag, and naronapride. All nine agents have shown prokinetic effects in different stages of the development. The mechanisms of new developing drugs include: the activation of 5-hydroxytryptamine type-4 (5-HT4), ghrelin and motilin receptors, antagonizing dopamine type-2 (D2) receptors, inhibition of ileal bile acid reabsorption and acetylcholine esterase, as well as water absorption from the GI tract.

Expert opinion: At this current point in time, new generations of 5-HT4 receptor agonists (velusetrag, noranopride and YKP10811) are hoped to progress, further in the future, due to better efficiency and safety. However, it is not possible to make a concise conclusion at this current time due to a lack of evidence. Further clinical trials with a longer duration and a larger sample size are warranted.

Comments:

Your introduction provides an overview of chronic constipation (CC) as a common gastrointestinal disorder that affects the quality of life of affected individuals. It also highlights the need for new medications with improved effectiveness and tolerability, as current options are not satisfactory for nearly half of the patients.

The article you mention focuses on experimental and clinical trials, up to Phase II, of new investigational drugs for the treatment of CC. It identifies nine agents: mitemcinal, TD-8954, YKP10811, itopride, RM-131, KWA-0711, elobixibat, velusetrag, and naronapride. These agents have demonstrated prokinetic effects at various stages of development. The mechanisms of action of these new drugs involve activating 5-hydroxytryptamine type-4 (5-HT4), ghrelin, and motilin receptors, antagonizing dopamine type-2 (D2) receptors, inhibiting ileal bile acid reabsorption and acetylcholine esterase, as well as reducing water absorption from the gastrointestinal tract.

According to expert opinion, the newer generations of 5-HT4 receptor agonists (velusetrag, noranopride, and YKP10811) hold promise for further progress in terms of efficacy and safety. However, due to a lack of sufficient evidence, a definitive conclusion cannot be drawn at this time. The author suggests that additional clinical trials with longer durations and larger sample sizes are needed to establish the efficacy and safety profiles of these new agents for CC treatment.