Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C20H21N3O.ClH.H2O |
Molecular Weight | 373.876 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O.Cl.CC1=NC=CN1C[C@H]2CCC3=C(C4=C5N3CCCC5=CC=C4)C2=O
InChI
InChIKey=JXQUEAGLZNCBHC-QCUBGVIVSA-N
InChI=1S/C20H21N3O.ClH.H2O/c1-13-21-9-11-22(13)12-15-7-8-17-18(20(15)24)16-6-2-4-14-5-3-10-23(17)19(14)16;;/h2,4,6,9,11,15H,3,5,7-8,10,12H2,1H3;1H;1H2/t15-;;/m1../s1
Developed by Solvay Pharmaceuticals, cilansetron is a 5-HT3 antagonist indicated for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS). 5-HT(3) receptor antagonists such as cilansetron have been shown to affect gastrointestinal motility. With Phase III registration trials on cilansetron completed, Solvay filed for regulatory approval in Europe and the US in 2004. To ensure that cilansetron is only prescribed to patients with diarrhoea-predominant IBS, Solvay’s regulatory submission included an extensive appropriate use plan. In April 2005, however, Solvay received a “non-approvable” letter from the FDA and a request for additional data to support product registration in the US. Towards the end of 2005, the company announced that it had suspended registration of cilansetron in the US. Meanwhile, discussions continue with the UK’s MHRA about European marketing approval for cilansetron. In 2005, the MHRA also declined to approve cilansetron. Both the agencies requested additional clinical data to further assess the risk-benefit ratio of the compound. Despite the drug being rejected for approval, Solvay believed in the product and felt that the clinical data demonstrated important benefits for men and women suffering from diarrhoea-predominant IBS. However, taking into account the amount of clinical work requested and other business considerations, the company decided to end the development and regulatory activities for cilansetron. The clinical efficacy and safety of cilansetron was established in a series of clinical trials, including a large-scale international Phase III programme involving over 4,000 patients. Overall, results from these trials showed that cilansetron is significantly more effective than placebo in male and female patients with diarrhoea-predominant IBS, an important finding given the traditionally high placebo response rates seen in clinical trials of IBS drugs. Overall responder rates (adequate relief in at least 50% of weekly responses) for patients treated with cilansetron ranged from 52% to 61% compared with 37% to 46% for placebo recipients. The most common side effect of cilansetron is constipation, which is seen in 3-12% of subjects at 6 months. Ischemic colitis, a side effect associated with previous drugs of this class, has been seen in eight subjects (six women and two men) to date. All of these ischemic colitis events have been self-limited and did not require surgery. Because of its high degree of efficacy, the fact that it was well tolerated by the overwhelming majority of patients and that it showed efficacy in both genders, cilansetron represented a major advance in the treatment of irritable bowel syndrome with diarrhea predominance.
Approval Year
PubMed
Title | Date | PubMed |
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Gateways to clinical trials. | 2002 Oct |
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[Visceral hypersensitivity: a concept within our reach]. | 2003 Jan |
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Irritable bowel syndrome: an overview of diagnosis and pharmacologic treatment. | 2003 Jun |
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Cilansetron: KC 9946. | 2005 |
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Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea. | 2005 Feb |
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Gateways to clinical trials. | 2005 Jan-Feb |
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Gateways to clinical trials. | 2005 May |
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Cilansetron. | 2005 Oct |
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Gateways to clinical trials. | 2005 Oct |
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Personal view: adequate relief as a primary endpoint in irritable bowel syndrome. | 2006 Apr 1 |
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Gateways to clinical trials. | 2006 Jan-Feb |
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Systematic review: the efficacy of treatments for irritable bowel syndrome--a European perspective. | 2006 Jul 15 |
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Pharmacological profile of ramosetron, a novel therapeutic agent for IBS. | 2007 Feb |
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Gateways to clinical trials. | 2007 Jan-Feb |
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Evaluation of the pharmacological profile of ramosetron, a novel therapeutic agent for irritable bowel syndrome. | 2007 Jul |
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[Irritable bowel syndrome: current treatment options]. | 2007 Nov |
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Effect of ramosetron on conditioned emotional stress-induced colonic dysfunction as a model of irritable bowel syndrome in rats. | 2007 Nov 14 |
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Effects of serotonin 5-HT(3) receptor antagonists on CRF-induced abnormal colonic water transport and defecation in rats. | 2008 Jun 10 |
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Lubiprostone: evaluation of the newest medication for the treatment of adult women with constipation-predominant irritable bowel syndrome. | 2010 Oct 27 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19072430
Two large efficacy and safety trials extending over 3 and 6 months revealed a superiority of cilansetron 2 mg orally three-times daily over placebo reflected by numbers needed to treat of 4.8 and 5.6, respectively, for the parameter proportion of patients reporting adequate symptom relief. Dose-ranging studies showed no dose-response relationship.
Route of Administration:
Oral
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C94726
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ACTIVE MOIETY
SUBSTANCE RECORD