Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C20H21N3O |
Molecular Weight | 319.4002 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=NC=CN1C[C@H]2CCC3=C(C4=C5N3CCCC5=CC=C4)C2=O
InChI
InChIKey=NCNFDKWULDWJDS-OAHLLOKOSA-N
InChI=1S/C20H21N3O/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/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 |
---|---|---|
Cilansetron. Solvay. | 2001 Oct |
|
[Visceral hypersensitivity: a concept within our reach]. | 2003 Jan |
|
Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea. | 2005 Feb |
|
Gateways to clinical trials. | 2005 Oct |
|
Systematic review: the efficacy of treatments for irritable bowel syndrome--a European perspective. | 2006 Jul 15 |
|
Gateways to clinical trials. | 2007 Jan-Feb |
|
Evaluation of the pharmacological profile of ramosetron, a novel therapeutic agent for irritable bowel syndrome. | 2007 Jul |
|
Cilansetron in the treatment of diarrhea-predominant irritable bowel syndrome? | 2007 Oct |
|
Serotonin receptor modulators in the treatment of irritable bowel syndrome. | 2008 Feb |
|
Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. | 2009 Jul |
|
Alosetron, cilansetron and tegaserod modify mesenteric but not colonic blood flow in rats. | 2009 Nov |
|
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
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NCI_THESAURUS |
C94726
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
||
|
WHO-VATC |
QA03AE03
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
||
|
WHO-ATC |
A03AE03
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
2J6DQ1U5B5
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
CHEMBL2103778
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
DTXSID40152951
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
m1069
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | Merck Index | ||
|
C084473
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
CILANSETRON
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
7007
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
120635-74-7
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
RR-35
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
DB04885
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
SUB06263MIG
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
100000081311
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
6918107
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY | |||
|
C76106
Created by
admin on Fri Dec 15 16:10:12 UTC 2023 , Edited by admin on Fri Dec 15 16:10:12 UTC 2023
|
PRIMARY |
ACTIVE MOIETY
SALT/SOLVATE (PARENT)