Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

Table 2 Chemical and clinical characteristics of discontinued/failed prokinetics

	Cisapride	Renzapride	Tegaserod
Chemical structure	Piperidinyl benzamide	Benzamide derivative	Indole carboxaldehyde derivative
Target receptors	Nonselective 5-HT4 agonist and 5-HT3 antagonist	Full 5-HT4 agonist and antagonist of 5-HT3 and 5-HT2b	5-HT4 and 5-HT1 partial agonist
Mechanism of action/pharmacodynamic effects	Local acetylcholine release;	Local acetylcholine release;	Augmentation of the peristaltic reflex;
	Acceleration of GI transit	Acceleration of GI transit	Enhanced intestinal secretion;
			Reduced sensitivity to rectal distension
Most common adverse events	Diarrhea	Diarrhea	Diarrhea
	Abdominal pain	Abdominal pain	Abdominal pain
		Headache	Headache
		Flatulence	Flatulence
Safety	Prolongation of QTc interval and fatal arrhythmias	No prolongation of QTc interval	Increased risk of serious ischemic cardiac events
Approval status	Approved in 1993; Withdrawn in 2000	Phase 3 RCTs terminated due to insufficient efficacy	Approved in 2002 for IBS-C (not in EU) and in 2004 for CC; Withdrawn in 2007

CC: Chronic constipation; EU: European Union; GI: Gastrointestinal; IBS-C: Constipation predominant-irritable bowel syndrome; QTc: Corrected QT interval; RCT: Randomized controlled trial; 5-HT: 5-hydroxytryptamine.