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. Author manuscript; available in PMC: 2011 Dec 1.
Published in final edited form as: Expert Rev Gastroenterol Hepatol. 2011 Feb;5(1):43–57. doi: 10.1586/egh.10.88

Table 2.

Effect of irritable bowel syndrome candidate compounds on preclinical (rodents) and clinical readouts of altered visceral sensitivity and gastrointestinal transit.

Receptor
targeted		 Compound Preclinical Clinical
Motility Visceral analgesial
anti-hyperalgesia 		Anxiety Transit Perception Brain imaging
for visceral pain 		IBS symptoms
(Phase II or III)
κ1-opioid Fedotozine
(agonist)		 ↑ transit after
ileus induced by
laparotomy or
irritation [42,43]		 Reduced visceral
hypersensitivity in a
model of colonic
irritation [44,45]
Antinociceptive
effect on duodenal
pain reflexes in
rats [46]		 NR NR ↓ gastric sensitivity to
to distension in
healthy humans [47]
Relieved
hypersensitivity
CRD in IBS
patients [15]		 NR Relief of abdominal
pain and bloating in
IBS patients
compared with
control. Effect on
transit not
reported [16]
μ-opioid Fentanyl
(agonist)		 ↓ Gl transit
[48–50]		 Prevented the
sensitizing response
associated to
repetitive CRD in
mice [51,52]		 Fentanyl
attenuated
fear-potentiated
startle in rats [53]
Anxiolytic effect
of central
μ-opioid agonist
on pain-induced
anxiety [54]		 Slowed Gl
transit [55]		 Attenuated the
perception of
phasic rectal
distension in IBS
patients [14]		 NR NR
5-HT3 Alosetron
(antagonist)		 Reduction of
colonic motility
[56]		 Centrally mediated
visceral anti-
hyperalgesic effect
[57,58]		 NR Reduction of
Gl transit [59]		 ↑ colonic
compliance
Lack of true
visceroanalgesic
effect [18]		 Changes in central
modulation of gut
function and
pain [60]		 Global improvement
of symptoms in
male and female
patients with
IBS-D [19]
5-HT4, 5-HT2b Tegaserod
(5-HT4agonist,
5-HT2b
antagonist)		 Enhanced Gl
motor function
[61]		 Reduction in visceral
sensitivity [62,63]		 NR Acceleration of
Gl transit [64]		 Generally no
evidence for
visceroanalgesic
effect [65,66]		 Modulation of
central processing
of visceral afferent
information [67]		 Effective in the
treatment of
constipation-
predominant IBS
symptoms [68]
5HT1A Robalzotan
tartrate
monohydrate		 Inhibition of
micturition [69]		 Reduction of the
visceromotor
response to CRD but
no change in the
pseudoaffective
cardiovascular
autonomic
response [69]		 NR No evidence
for changes in
bowel
movements [70]		 No evidence for
changes in
abdominal
discomfort or
pain [70]		 NR Not more effective
than placebo in
providing adequate
relief from IBS
symptoms [70]
Somatostatin Octreotide
(agonist)		 Reduction of Gl
transit time [71]		 Visceroanalgesic
effect [72]		 NR Reduction of
Gl transit time
[73]		 Visceroanalgesic &
antihyperalgesic
effect during rectal
distension
[33,36,74–76]		 NR Overall symptom
improvement [77]
CCK1 Dexloxiglumide
(antagonists)		 Accelerates
transit time [78]		 ↓ sensitivity to CRD
in rats with inflamed
colon [79]		 NR Accelerates
transit time [80 		NR NR NR: therapeutic
effect not
confirmed [201]
NK3 Talnetant
(antagonist)		 Inhibits motility,
reduces
excitatory reflex
induced by
stretch in the
colon [81]		 Anti-hyperalgesic
effect [81]		 Anxiolytic effect
[82]		 NR Under evaluation
(unpublished)		 NR NR

↑: Increased; ↓: Decreased; 5-HT: Serotonin; CRD: Colorectal distension; Gl: Gastrointestinal; IBS: Irritable bowel syndrome; IBS-D: Diarrhea-predominant irritable bowel syndrome; NR: Not reported