Selective 5-Hydroxytryptamine Type 3 Receptor Antagonism With Ondansetron as Treatment for Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Study

Steadman, Charles; Talley, Nicholas J.; Phillips, Sidney F.; Zinsmeister, Alan R.

doi:10.1016/s0025-6196(12)60797-6

Cited by 104 publications

(63 citation statements)

References 22 publications

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“…Like in NUD patients, the benefit of 5-HT 3 receptor antagonists has not been evaluated in large clinical trials in patients with irritable bowel syndrome. The results of studies with small patient numbers are conflicting, but of course some reports show promising results [13, 25, 26]. …”

Section: Discussionmentioning

confidence: 99%

Effects of Tropisetron, a 5-HT<sub>3</sub> Receptor Antagonist, on Proximal Gastric Motor and Sensory Function in Nonulcer Dyspepsia

Klatt

Bock²,

Rentschler³

et al. 1999

Digestion

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Background: Visceral hypersensitivity is claimed to be involved in the pathogenesis of nonulcer dyspepsia (NUD). In a double-blind crossover study, we evaluated the effects of tropisetron, a 5-HT₃ receptor antagonist, on gastric accommodation, reflex relaxation, and sensitivity in NUD patients. Methods: Eight patients and 10 healthy controls received placebo or 5 mg tropisetron on separate days. On each day, gastric accommodation and relaxation were investigated using a gastric barostat. The perception during gastric distension and relaxation was scored by a verbal perception score. Results: Under both medications, gastric accommodation and postprandial gastric reflex relaxation were not impaired in the NUD patients. The visceral perception was increased in the NUD patients and not substantially influenced by tropisetron. Conclusions: Tropisetron does not influence gastric accommodation, reflex relaxation, or gastric sensitivity in NUD patients and healthy controls.

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Section: Discussionmentioning

confidence: 99%

Effects of Tropisetron, a 5-HT<sub>3</sub> Receptor Antagonist, on Proximal Gastric Motor and Sensory Function in Nonulcer Dyspepsia

Klatt

Bock²,

Rentschler³

et al. 1999

Digestion

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“…43,44 Furthermore, clinical trials of ondansetron on diarrhoea-predominant irritable bowel syndrome have been rather disappointing. 40,41 Thus, there is currently a strong need for more effective forms of therapy for irritable bowel syndrome particularly as it represents such a large work load for gastroenterologists as well as primary care physicians. 45±47 The results of this study show that a selective M 3 receptor antagonist can signi®cantly inhibit food-stimulated distal colonic motility with relatively minor anticholinergic side-effects.…”

Section: Discussionmentioning

confidence: 99%

Zamifenacin (UK‐76, 654), a potent gut M₃ selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome

Houghton¹,

Rogers

Whorwell³

et al. 1997

Aliment Pharmacol Ther

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The pathophysiology of irritable bowel syndrome is poorly understood, but studies have suggested that disordered motility of both the small 1±3 and large bowel, 4±8 and abnormalities in gut visceral sensation, 9±15 may play important roles. The most consistent motor abnormality in the small bowel is a marked increase in`cluster activity' seen in the wakeful state but not during sleep, 1±3 whilst in the colon motility in many patients appears to be exaggerated, particularly after meals. 4±8 The main defect of visceral sensation appears to be hypersensitivity, and this has been demonstrated in the entire length of the gastrointestinal tract in patients with irritable bowel syndrome. 3, 9±15 Current therapy is far from satisfactory, ranging from modi®cations in diet to pharmacological intervention. SUMMARYBackground: Zamifenacin is a new potent gut M 3 selective muscarinic antagonist developed for possible use in irritable bowel syndrome. Methods: In this multicentre, double-blind, parallel group, placebo-controlled study, the effect of a single dose of zamifenacin 10 mg or 40 mg on both fasting (30 min) and fed (60 min) colonic motor activity was assessed in 36 patients with irritable bowel syndrome (aged 25±68 years; 19 male). Colonic motility was recorded using a ®ve-channel solid-state catheter introduced by colonoscopy to a depth of 35 cm in an unprepared colon. Results: Zamifenacin 40 mg profoundly reduced colonic motility, particularly after the meal (P < 0.05). This was re¯ected by a signi®cant reduction in the mean amplitude of contractions, number of contractions,

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“…It has already been reported (26) that wrap-restraint stress-induced defecation is in hibited by granisetron and ondansetron. However, the effects of 5-HT3-receptor antagonists on the wrap-re straint stress-induced propulsive motility of the proximal and the distal colon have never been reported prior to the the diarrhea associated with IBS (27,28). The present study indicated that the doses of KF18259 to inhibit wrap-restraint stress-induced defecation were lower than those to inhibit the 5-HT-induced von Bezold Jarisch reflex and the cisplatin-induced slowing of gastric emptying.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Properties of KF18259, a Novel 5-HT3-Receptor Antagonist, in Rats: Inhibition of the Distal Colonic Function

Kishibayashi

Ichikawa

Yokoyama

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the effects of KF18259 (endo-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-1 isobutyl-2-oxo-1,2-dihydro-4-quinolinecarboxylate hydrochloride), a novel 5-HT3-receptor antagonist, in a variety of rat models, which are assumed to be mediated via 5-HT3 receptors, in comparison with those of5,6,7-tetrahydro-1H-benzimidazole hydrochloride), granisetron and ondansetron. KF18259 inhibited wrap-restraint stress-induced defecation. The doses of KF 18259 to inhibit wrap-restraint stress-induced defecation were lower than those to inhibit the 5-HT-in duced von Bezold-Jarisch reflex and the cisplatin-induced slowing of gastric emptying. In contrast, the doses of YM060, granisetron and ondansetron to inhibit these three responses were similar. Moreover, KF18259 inhibited the wrap-restraint stress-induced propulsive motility of the proximal and distal colon. The effect of KF18259 on the distal colon was as potent as that on defecation and was more potent than that on the prox imal colon. These results indicate that KF18259 potently inhibits the distal colonic function. KF18259 may be a useful tool for the discrimination of the 5-HT3-receptors located on the distal colon and other tissues.

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Selective 5-Hydroxytryptamine Type 3 Receptor Antagonism With Ondansetron as Treatment for Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Study

Cited by 104 publications

References 22 publications

Effects of Tropisetron, a 5-HT<sub>3</sub> Receptor Antagonist, on Proximal Gastric Motor and Sensory Function in Nonulcer Dyspepsia

Effects of Tropisetron, a 5-HT<sub>3</sub> Receptor Antagonist, on Proximal Gastric Motor and Sensory Function in Nonulcer Dyspepsia

Zamifenacin (UK‐76, 654), a potent gut M₃ selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome

Pharmacological Properties of KF18259, a Novel 5-HT3-Receptor Antagonist, in Rats: Inhibition of the Distal Colonic Function

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Selective 5-Hydroxytryptamine Type 3 Receptor Antagonism With Ondansetron as Treatment for Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Study

Cited by 104 publications

References 22 publications

Effects of Tropisetron, a 5-HT<sub>3</sub> Receptor Antagonist, on Proximal Gastric Motor and Sensory Function in Nonulcer Dyspepsia

Effects of Tropisetron, a 5-HT<sub>3</sub> Receptor Antagonist, on Proximal Gastric Motor and Sensory Function in Nonulcer Dyspepsia

Zamifenacin (UK‐76, 654), a potent gut M3 selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome

Pharmacological Properties of KF18259, a Novel 5-HT3-Receptor Antagonist, in Rats: Inhibition of the Distal Colonic Function

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Zamifenacin (UK‐76, 654), a potent gut M₃ selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome