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| Approval status | Approved in 1993; Withdrawn in 2000 | Phase 3 RCTs terminated due to insufficient efficacy | Approved in 2002 for IBS-C (not in EU) and in 2004 for CC; Withdrawn in 2007 |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.