Cilansetron

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Name
Cilansetron
Accession Number
DB04885
Type
Small Molecule
Groups
Investigational
Description

Cilansetron is a 5HT-3 antagonist made by Solvay Pharmaceuticals that is currently under trial phase in the EU and US.

Structure
Thumb
Synonyms
Not Available
External IDs
KC-9946
International/Other Brands
Calmactin
Categories
UNII
2J6DQ1U5B5
CAS number
120635-74-7
Weight
Average: 319.4002
Monoisotopic: 319.168462309
Chemical Formula
C20H21N3O
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[7.6.1.0⁵,¹⁶.0¹⁰,¹⁵]hexadeca-5(16),6,8,10(15)-tetraen-11-one
SMILES
CC1=NC=CN1C[C@H]1CCC2=C(C3=CC=CC4=C3N2CCC4)C1=O

Pharmacology

Indication

For the treatment of symptoms associated with irritable bowel syndrome.

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 Alosetron, also a 5-HT3 antagonist, was withdrawn from the market due to questions regarding its safety.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.

TargetActionsOrganism
U5-hydroxytryptamine receptor 3ANot AvailableHumans
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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.
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Cilansetron is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Cilansetron is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Cilansetron is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Cilansetron.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Cilansetron is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Cilansetron.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Cilansetron is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Cilansetron.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Cilansetron is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcenocoumarolThe risk or severity of adverse effects can be increased when Cilansetron is combined with Acenocoumarol.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:15757394]
  2. Authors unspecified: Cilansetron: KC 9946. Drugs R D. 2005;6(3):169-73. [PubMed:15869320]
  3. 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. [PubMed:16842448]
External Links
KEGG Drug
D03495
PubChem Compound
6918107
PubChem Substance
175426888
ChemSpider
5293321
BindingDB
50231569
ChEMBL
CHEMBL2103778
Wikipedia
Cilansetron
ATC Codes
A03AE03 — Cilansetron

Clinical Trials

Clinical Trials
Not Available

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
PropertyValueSource
Water Solubility0.115 mg/mLALOGPS
logP2.47ALOGPS
logP2.83ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)15.48ChemAxon
pKa (Strongest Basic)7.34ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area39.82 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity94.69 m3·mol-1ChemAxon
Polarizability35.88 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9951
Blood Brain Barrier+0.9741
Caco-2 permeable+0.7249
P-glycoprotein substrateSubstrate0.7409
P-glycoprotein inhibitor IInhibitor0.7613
P-glycoprotein inhibitor IIInhibitor0.8408
Renal organic cation transporterInhibitor0.8412
CYP450 2C9 substrateNon-substrate0.74
CYP450 2D6 substrateSubstrate0.752
CYP450 3A4 substrateSubstrate0.5146
CYP450 1A2 substrateInhibitor0.7238
CYP450 2C9 inhibitorNon-inhibitor0.661
CYP450 2D6 inhibitorInhibitor0.62
CYP450 2C19 inhibitorNon-inhibitor0.5519
CYP450 3A4 inhibitorNon-inhibitor0.6399
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7631
Ames testNon AMES toxic0.5587
CarcinogenicityNon-carcinogens0.9727
BiodegradationNot ready biodegradable0.9935
Rat acute toxicity2.5384 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6121
hERG inhibition (predictor II)Inhibitor0.6571
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Carbazole / Indole / Aryl ketone / Aryl alkyl ketone / N-substituted imidazole / Benzenoid / Azole / Imidazole / Pyrrole / Heteroaromatic compound
show 11 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

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
  1. 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. [PubMed:15757394]
  2. Komoto S, Miura S: [Antagonists of the type 3 serotonin receptor (5 -HT3) in IBS]. Nihon Rinsho. 2006 Aug;64(8):1487-90. [PubMed:16898618]

Drug created on October 21, 2007 06:21 / Updated on November 02, 2019 01:47