. Author manuscript; available in PMC: 2014 Aug 12.

Published in final edited form as: Gut. 2007 Oct 26;57(3):384–404. doi: 10.1136/gut.2006.101675

Table 3.

Effect of candidate compounds and preclinical and clinical read outs

Receptor targeted	Compound	Preclinical			Clinical
Receptor targeted	Compound	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 irritation^144,145	Reduced visceral hypersensitivity in a model of colonic irritation^146,147 Antinociceptive effect on duodenal pain reflexes in rats¹⁴⁸	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
μ-opioid	Fentanyl (agonist)	Decreased GI transit^150–152	Prevented the sensitisation associated with repetitive colorectal distensions in mice^120,122	Fentanyl attenuated fear-potentiated startle in rats¹⁵³ Anxiolytic effect of central μ-opioid agonist on pain-induced anxiety¹⁵⁴	Slowed GI transit¹⁵⁵	Attenuated the perception of phasic rectal distension in IBS patients⁴⁰	NR	NR
5-HT₃	Alosetron (antagonist)	Reduction of colonic motility¹⁵⁶	Centrally mediated visceral antihyperalgesic effect^157,158	NR	Reduction of GI transit¹⁰²	Increased colonic compliance. Lack of true visceroanalgesic effect⁵¹	Changes in central modulation of gut function and pain^159,160	Global improvement of symptoms in male and female patients with IBS-D⁵²
5-HT₄	Tegaserod (agonist)	Enhanced GI motor function¹⁶¹	Reduction in visceral sensitivity^162,163	NR	Acceleration of GI transit¹⁰⁴	Generally no evidence for visceroanalgesic effect^74,164	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 distension^{67,70,170–172}	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 effect^176,177	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.