Cilansetron
Identification
- Generic Name
- Cilansetron
- DrugBank Accession Number
- DB04885
- Background
Cilansetron is a 5HT-3 antagonist made by Solvay Pharmaceuticals that is currently under trial phase in the EU and US.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 319.4002
Monoisotopic: 319.168462309 - Chemical Formula
- C20H21N3O
- Synonyms
- Cilansetron
- External IDs
- KC-9946
Pharmacology
- Indication
For the treatment of symptoms associated with irritable bowel syndrome.
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- Pharmacodynamics
Cilansetron is an orally formulated medication that blocks the action of 5-hydroxy-tryptamine 3 (5-HT3) receptors. Phase III studies of cilansetron had been suspended by Solvay in order to assess whether the drug possesses safety concerns similar to alosetron. Alosetron, also a 5-HT3 antagonist, was withdrawn from the market due to questions regarding its safety. Phase III testing with cilansetron has since resumed. In June 2005 the company announced that they were reviewing the priority of the cilansetron program.
- Mechanism of action
Cilansetron is a potent and selective 5-HT3 receptor antagonist. 5-HT3 receptors are nonselective cation channels that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit and gastrointestinal secretions, processes that relate to the pathophysiology of irritable bowel syndrome (IBS). 5-HT3 receptor antagonists such as cilansetron inhibit activation of non-selective cation channels which results in the modulation of the enteric nervous system.
Target Actions Organism U5-hydroxytryptamine receptor 3A Not Available Humans - Absorption
Rapidly absorbed orally with a bioavailability of greater than 80% in rats.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
The elimination half-life after 4- and 8-mg oral doses administered 3 times daily for 6 days was reported to be 1.6 to 1.9 hours.
- Clearance
Not Available
- Adverse Effects
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- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Cilansetron is combined with 1,2-Benzodiazepine. Acenocoumarol The risk or severity of adverse effects can be increased when Cilansetron is combined with Acenocoumarol. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Cilansetron. Acetophenazine The risk or severity of CNS depression can be increased when Acetophenazine is combined with Cilansetron. Agomelatine The risk or severity of CNS depression can be increased when Cilansetron is combined with Agomelatine. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Calmactin
Categories
- ATC Codes
- A03AE03 — Cilansetron
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Carbazoles
- Direct Parent
- Carbazoles
- Alternative Parents
- Indoles / Aryl alkyl ketones / N-substituted imidazoles / Benzenoids / Vinylogous amides / Pyrroles / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds show 2 more
- Substituents
- Aromatic heteropolycyclic compound / Aryl alkyl ketone / Aryl ketone / Azacycle / Azole / Benzenoid / Carbazole / Heteroaromatic compound / Hydrocarbon derivative / Imidazole show 11 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 2J6DQ1U5B5
- CAS number
- 120635-74-7
- InChI Key
- NCNFDKWULDWJDS-OAHLLOKOSA-N
- InChI
- 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
- IUPAC Name
- (12R)-12-[(2-methyl-1H-imidazol-1-yl)methyl]-1-azatetracyclo[7.6.1.0^{5,16}.0^{10,15}]hexadeca-5(16),6,8,10(15)-tetraen-11-one
- SMILES
- CC1=NC=CN1C[C@H]1CCC2=C(C3=CC=CC4=C3N2CCC4)C1=O
References
- General References
- Chey WD, Cash BD: Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea. Expert Opin Investig Drugs. 2005 Feb;14(2):185-93. [Article]
- Authors unspecified: Cilansetron: KC 9946. Drugs R D. 2005;6(3):169-73. [Article]
- Tack J, Fried M, Houghton LA, Spicak J, Fisher G: Systematic review: the efficacy of treatments for irritable bowel syndrome--a European perspective. Aliment Pharmacol Ther. 2006 Jul 15;24(2):183-205. [Article]
- External Links
- KEGG Drug
- D03495
- PubChem Compound
- 6918107
- PubChem Substance
- 175426888
- ChemSpider
- 5293321
- BindingDB
- 50231569
- ChEMBL
- CHEMBL2103778
- Wikipedia
- Cilansetron
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.115 mg/mL ALOGPS logP 2.47 ALOGPS logP 2.83 Chemaxon logS -3.4 ALOGPS pKa (Strongest Acidic) 16.16 Chemaxon pKa (Strongest Basic) 7.34 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 39.82 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 94.69 m3·mol-1 Chemaxon Polarizability 35.88 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9951 Blood Brain Barrier + 0.9741 Caco-2 permeable + 0.7249 P-glycoprotein substrate Substrate 0.7409 P-glycoprotein inhibitor I Inhibitor 0.7613 P-glycoprotein inhibitor II Inhibitor 0.8408 Renal organic cation transporter Inhibitor 0.8412 CYP450 2C9 substrate Non-substrate 0.74 CYP450 2D6 substrate Substrate 0.752 CYP450 3A4 substrate Substrate 0.5146 CYP450 1A2 substrate Inhibitor 0.7238 CYP450 2C9 inhibitor Non-inhibitor 0.661 CYP450 2D6 inhibitor Inhibitor 0.62 CYP450 2C19 inhibitor Non-inhibitor 0.5519 CYP450 3A4 inhibitor Non-inhibitor 0.6399 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7631 Ames test Non AMES toxic 0.5587 Carcinogenicity Non-carcinogens 0.9727 Biodegradation Not ready biodegradable 0.9935 Rat acute toxicity 2.5384 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.6121 hERG inhibition (predictor II) Inhibitor 0.6571
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0079-0090000000-fb4b669e46b1181723a4 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0009000000-e7f33aab710912c1a540 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0079-0093000000-fd2a5792e7589dd1b715 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0093000000-8a867377266cc452481a Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00b9-0191000000-3ef2f963e8397607a756 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001r-3491000000-0681fa41503574d165f1 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 186.2629137 predictedDarkChem Lite v0.1.0 [M-H]- 173.43571 predictedDeepCCS 1.0 (2019) [M+H]+ 186.2305137 predictedDarkChem Lite v0.1.0 [M+H]+ 175.79385 predictedDeepCCS 1.0 (2019) [M+Na]+ 186.2533137 predictedDarkChem Lite v0.1.0 [M+Na]+ 181.90102 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Voltage-gated potassium channel activity
- Specific Function
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gate...
- Gene Name
- HTR3A
- Uniprot ID
- P46098
- Uniprot Name
- 5-hydroxytryptamine receptor 3A
- Molecular Weight
- 55279.835 Da
References
Drug created at October 21, 2007 12:21 / Updated at February 21, 2021 18:51