Several 5-HT4 receptor (5-HT4R) agonists are approved for treating chronic idiopathic constipation (CIC) by stimulating gastrointestinal (GI) motility. Traditional 5-HT4R agonists act systemically, causing central nervous and cardiovascular side effects. In contrast, gut-restricted agonists like prucalopride target the GI tract, reducing these risks.