Motility disorders, gastrointestinal constipation

In the periphery, 5-HT4 receptor mRNA is found in vascular smooth muscle. Newly developed drugs that activate 5-HT4 receptors are of interest for their potential in treating cardiac arrhythmia. The 5-HT4 receptor is also located on neurons of the alimentary tract, for example the myenteric plexus of the ileum, and on smooth muscle cells and secretory cells of the gastrointestinal tract, where they evoke secretions and the peristaltic reflex. 5-HT4 receptor agonists (e.g. cisapride, prucalopride, tegaserod) are used therapeutically in the treatment of constipation-predominant irritable bowel syndrome and in functional motility disorders of the upper gastrointestinal tract. 

Benzamides are already used as therapeutic prokinetic agents. They are of benefit in many gastrointestinal motility disorders, such as gastroesophageal reflux, non-ulcer dyspepsia gastroparesis and constipation [110, 111]. 

Pathophysiologically, constipation generally results from disordered colonic transit or anorectal function as a result of a primary motility disturbance, certain drugs, or in association with a large number of systemic diseases that affect the gastrointestinal tract. Constipation from any cause may be exacerbated by chronic illnesses that lead to physical or mental impairment and result in inactivity or physical immobility. Additional contributing factors may include a lack of fiber in the diet, generalized muscle weakness, and possibly stress and anxiety. 

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