| Receptor targeted | Compound | Preclinical | Clinical | |||||
| Motility | Visceral analgesia/antihyperalgesia | Anxiety | Transit | Perception | Brain imaging for visceral pain | IBS symptoms (phase II or III) | ||
| κ1-opioid | Fedotozine (agonist) | Increased transit after ileus induced by laparotomy or irritation144 145 | Reduced visceral hypersensitivity in a model of colonic irritation146 147 | NR | NR | Decreased gastric sensitivity to distension in healthy humans149 Relieved hypersensitivity to colorectal distension in IBS patients48 | NR | Relief of abdominal pain and bloating in IBS patients compared with control. Effect on transit not reported49 |
| Antinociceptive effect on duodenal pain reflexes in rats148 | ||||||||
| μ-opioid | Fentanyl (agonist) | Decreased GI transit150–152 | Prevented the sensitisation associated with repetitive colorectal distensions in mice120 122 | Fentanyl attenuated fear-potentiated startle in rats153 | Slowed GI transit155 | Attenuated the perception of phasic rectal distension in IBS patients40 | NR | NR |
| Anxiolytic effect of central μ-opioid agonist on pain-induced anxiety154 | ||||||||
| 5-HT3 | Alosetron (antagonist) | Reduction of colonic motility156 | Centrally mediated visceral antihyperalgesic effect157 158 | NR | Reduction of GI transit102 | Increased colonic compliance. Lack of true visceroanalgesic effect51 | Changes in central modulation of gut function and pain159 160 | Global improvement of symptoms in male and female patients with IBS-D52 |
| 5-HT4 | Tegaserod (agonist) | Enhanced GI motor function161 | Reduction in visceral sensitivity162 163 | NR | Acceleration of GI transit104 | Generally no evidence for visceroanalgesic effect74 164 | Modulation of central processing of visceral afferent information165 | Effective in the treatment of IBS-C symptoms166 |
| Somatostatin 2,3,5 | Octreotide (agonist) | Reduction of GI transit time167 | Visceroanalgesic effect168 | NR | Reduction of GI transit time169 | Visceroanalgesic and antihyperalgesic effect during rectal distension67 70 170–172 | NR | Overall symptom improvement68 |
| CCK-1 | Dexloxiglumide (antagonists) | Accelerated transit time173 | Decreased sensitivity to colorectal distension in rats with inflamed colon174 | NR | + accelerates transit time101 | NR | NR | NR: Press release, Forest, 1 October 2003: therapeutic effect not confirmed |
| NK3 | Talnetant (antagonist) | Inhibited motility, reduced excitatory reflex induced by stretch in the colon175 | Antihyperalgesic effect175 | Anxiolytic effect176 177 | NR | No effect in healthy controls61 | NR | No effect compared with placebo60 |
CCK, cholecystokinin; GI, gastrointestinal; IBS, irritable bowel syndrome; IBS-C, constipation-predominant irritable bowel syndrome; IBS-D, diarrhoea-predominant irritable bowel syndrome; NR, data not reported.