Cilansetron shows efficacy in male and female non-constipated patients with irritable bowel syndrome in a United States study

Caras, Steven; Krause, G; Biesheuvel, Egbert; Steinborn, Claus

doi:10.1016/s0016-5085(08)81078-5

Cited by 25 publications

(13 citation statements)

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“…At present, IBS is treated with spasmolytic agents (anti-cholinergic drugs), anti-diarrheal agents (opioid receptor agonists), lactobacillus preparations, and polymer formulations, but there is insufficient evidence to support their effectiveness (20). Recently, several 5-HT 3 -receptor antagonists, such as alosetron (11), cilansetron (12), and ramosetron, have been developed for treatment of IBS-D, and it is anticipated that they will be clinically effective. In this study, we therefore aimed to compare the pharmacological profiles of these drugs.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the dissociation of alosetron and cilansetron from human 5-HT 3 receptors was relatively fast, with t 1/ 2 values of 180 and 88 min, respectively. In clinical trials, alosetron (11) and cilansetron (12) were shown to improve the symptoms of IBS-D with dosing frequencies of two and three times a day, respectively. These results, and literature reports, all suggest that ramosetron may exhibit a longer duration of 5-HT 3 -receptor antagonism than does alosetron or cilansetron, and ramosetron may be expected to significantly improve the symptoms of IBS-D at a low dosing frequency (perhaps once a day).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, several 5-HT 3 -receptor antagonists such as alosetron (11) and cilansetron (12) have been developed for IBS-D. However, no study has been performed to directly compare the potencies of these drugs.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Pharmacological Profile of Ramosetron, a Novel Therapeutic Agent for Irritable Bowel Syndrome

et al. 2007

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Abstract. We examined the pharmacological profile of ramosetron, a 5-HT 3 -receptor antagonist for irritable bowel syndrome with diarrhea, comparing it with those of other 5-HT 3 -receptor antagonists, alosetron and cilansetron, and the anti-diarrheal agent loperamide. Ramosetron showed high affinity for cloned human and rat 5-HT 3 receptors, with K i values of 0.091 ± 0.014 and 0.22 ± 0.051 nmol / L, respectively, while its affinities for other receptors, transporters, ion channels, and enzymes were negligible. Dissociation of ramosetron from the human 5-HT 3 receptor was extremely slow (t 1/ 2 = 560 min), while alosetron (t 1/ 2 = 180 min) and cilansetron (t 1/ 2 = 88 min) dissociated relatively rapidly. Ramosetron competitively inhibited 5-HT-induced contraction of isolated guinea-pig colon, with pA 2 values of 8.6 (8.5 -9.0). Ramosetron given orally also dose-dependently inhibited the von Bezold-Jarisch reflex in rats, with an ED 50 value of 1.2 (0.93 -1.6) µg / kg. In addition, oral ramosetron dose-dependently inhibited restraint stressinduced defecation in rats, with an ED 50 value of 0.62 (0.17 -1.2) µg/ kg. In all of these experiments, the potencies of ramosetron were greater than those of alosetron, cilansetron, or loperamide. These results indicate that ramosetron is a highly potent and selective 5-HT 3 -receptor antagonist, with beneficial effects against stress-induced abnormal defecation in rats.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evaluation of the Pharmacological Profile of Ramosetron, a Novel Therapeutic Agent for Irritable Bowel Syndrome

et al. 2007

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“…Cilansetron is a 5-HT 3 receptor antagonist with very similar pharmacodynamic properties as alosetron. It appeared effective in male and female patients with nonconstipated IBS at 1-and 16-mg doses [17,18] . Agonists of the 5-HT 4 receptors display a prokinetic effect in the gut, as they promote motility and transit.…”

Section: Serotoninergic Agentsmentioning

confidence: 99%

Drugs Affecting Visceral Sensitivity: Ready for the Prime Time?

Delvaux

2006

Dig Dis

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Visceral sensitivity has been recognized over the last decade as a frequent pathophysiological component of functional bowel disorders. Studies in animals and humans have identified numerous neurotransmitters involved in the processing of sensations from the gut to the brain. However, up to now none of them has actually been proven to have a marked clinical efficacy and the benefit comes rather from their action of bowel disturbances. Reproducible tests are lacking to detect visceral hypersensitivity in humans and distension tests are difficult to undertake in a clinical setting. Therefore, abnormal visceral sensitivity may not be regarded as a tool to select IBS patients as candidates for a given treatment.

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“…In contrast, several serotonin (5-HT) 3 -receptor antagonists have recently been developed as therapeutic agents for IBS-D, and their effectiveness has now been established (4,5). It has been reported that 5-HT 3 receptors are widely distributed within the gastrointestinal tract, and activation of these receptors by endogenous 5-HT results in intestinal secretion and peristaltic activity (6).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Ramosetron, a Potent and Selective 5-HT3–Receptor Antagonist, on Conditioned Fear Stress–Induced Abnormal Defecation and Normal Defecation in Rats: Comparative Studies With Antidiarrheal and Spasmolytic Agents

et al. 2008

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Abstract. We examined the effect of ramosetron, a potent serotonin (5-HT) 3 -receptor antagonist for irritable bowel syndrome with diarrhea, on conditioned fear stress (CFS)-induced defecation and normal (non-stressed) defecation in rats and compared ramosetron with the antidiarrheal agent loperamide and the spasmolytic agents trimebutine and tiquizium. Ramosetron, loperamide, trimebutine, and tiquizium significantly inhibited CFS-induced defecation in a dose-dependent manner with ED 50 (95% confidence limit) values of 0.019 (0.01 -0.028), 9.4 (4.0 -22), 850 (520 -2,400), and 300 (190 -450) mg/ kg, respectively. A significant effect of ramosetron on CFS-induced defecation appeared at 10 min after dosing and was sustained for 8 h. In contrast, loperamide, trimebutine, and tiquizium significantly inhibited CFS-induced defecation between 1 -8, 1 -4, and 1 -8 h after administration, respectively. High doses of ramosetron did not affect normal defecation, whereas loperamide, trimebutine, and tiquizium significantly inhibited this process. In conclusion, ramosetron has potent, rapid-onset, and long-lasting inhibitory effects on CFS-induced defecation in rats, but does not influence normal defecation. The present findings indicate that ramosetron will be a useful therapeutic agent for irritable bowel syndrome with diarrhea, showing greater efficacy and safety than other antidiarrheal and spasmolytic agents.

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Cilansetron shows efficacy in male and female non-constipated patients with irritable bowel syndrome in a United States study

Cited by 25 publications

References 0 publications

Evaluation of the Pharmacological Profile of Ramosetron, a Novel Therapeutic Agent for Irritable Bowel Syndrome

Evaluation of the Pharmacological Profile of Ramosetron, a Novel Therapeutic Agent for Irritable Bowel Syndrome

Drugs Affecting Visceral Sensitivity: Ready for the Prime Time?

Inhibitory Effects of Ramosetron, a Potent and Selective 5-HT3–Receptor Antagonist, on Conditioned Fear Stress–Induced Abnormal Defecation and Normal Defecation in Rats: Comparative Studies With Antidiarrheal and Spasmolytic Agents

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