Identification

Name
Tropisetron
Accession Number
DB11699
Type
Small Molecule
Groups
Approved, Investigational
Description

Tropisetron is an indole derivative with antiemetic activity. As a selective serotonin receptor antagonist, tropisetron competitively blocks the action of serotonin at 5HT3 receptors, resulting in suppression of chemotherapy-and radiotherapy-induced nausea and vomiting.

Tropisetron appears to be well tolerated with the most frequently reported adverse effect being headache. Extrapyramidal side effects are rare upon using tropisetron.

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Tropisetron HydrochlorideA19338Q2YO105826-92-4XIEGSJAEZIGKSA-LUNMCBQDSA-N
Tropisetron MesylateX2V6FDY03T833482-77-2FFTYLXTULVZQRZ-LUNMCBQDSA-N
Categories
UNII
6I819NIK1W
CAS number
89565-68-4
Weight
Average: 284.3529
Monoisotopic: 284.152477894
Chemical Formula
C17H20N2O2
InChI Key
ZNRGQMMCGHDTEI-ITGUQSILSA-N
InChI
InChI=1S/C17H20N2O2/c1-19-11-6-7-12(19)9-13(8-11)21-17(20)15-10-18-16-5-3-2-4-14(15)16/h2-5,10-13,18H,6-9H2,1H3/t11-,12+,13+
IUPAC Name
(1R,3R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl 1H-indole-3-carboxylate
SMILES
[H][C@]12CC[C@]([H])(C[C@@]([H])(C1)OC(=O)C1=CNC3=CC=CC=C13)N2C

Pharmacology

Indication

For the prevention of nausea and vomiting induced by cytotoxic therapy and postoperative.

Pharmacodynamics
Not Available
Mechanism of action

Tropisetron competitively binds to and blocks the action of serotonin at 5HT3 receptors peripherally on vagus nerve terminals located in the gastrointestinal (GI) tract as well as centrally in the chemoreceptor trigger zone (CTZ) of the area postrema of the central nervous system (CNS). This results in the suppression of chemotherapy- and radiotherapy-induced nausea and vomiting.

TargetActionsOrganism
A5-hydroxytryptamine receptor 3A
antagonist
Human
Absorption

The absorption of tropisetron from the gastrointestinal tract is rapid (mean half-life of about 20 minutes) and nearly complete (more than 95%). Due to first-pass metabolism in the liver, the absolute bioavailability of a 5 mg oral dose is 60%. The peak plasma concentration is attained within three hours.

Volume of distribution

400-600 L.

Protein binding

71% bound to plasma protein in a non-specific manner.

Metabolism

The metabolism of tropisetron occurs by hydroxylation at the 5, 6 or 7 positions of its indole ring, followed by a conjugation reaction to the glucuronide or sulphate with excretion in the urine or bile (urine to faeces ratio 5:1). The metabolites have a greatly reduced potency for the 5-HT3 receptor and do not contribute to the pharmacological action of the drug.

Route of elimination

About 8% of tropisetron is excreted in the urine as unchanged drug, 70% as metabolites; 15% is excreted in the feces.

Half life

5.7 h.

Clearance

1800 ml/min.

Toxicity

LD50: 265 mg/kg (Rat, oral).

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*1XNNot AvailableNormal allele duplicated.ADR InferredUltra-rapid drug metabolizer. Risk of toxicity, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*2XNNot Available2850C>T / 4180G>C  … show all ADR InferredUltra-rapid drug metabolizer. Risk of toxicity, alternative drug recommended.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Tropisetron is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Tropisetron is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Tropisetron is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Tropisetron.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Tropisetron.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Tropisetron is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Tropisetron.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Tropisetron 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 Tropisetron.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Tropisetron.
Food Interactions
Not Available

References

General References
  1. product info [Link]
  2. Monograph [Link]
  3. MSDS [Link]
  4. Article [Link]
External Links
KEGG Compound
C13666
PubChem Compound
656665
PubChem Substance
347828064
ChemSpider
16736476
BindingDB
50108392
ChEBI
32269
ChEMBL
CHEMBL56564
HET
TKT
Wikipedia
Tropisetron
ATC Codes
A04AA03 — Tropisetron
PDB Entries
2wnc / 5oaj

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedSupportive CareNausea and vomiting / Unspecified Adult Solid Tumor, Protocol Specific1
2CompletedTreatmentDisease, Chronic / Pain NOS1
2Unknown StatusPreventionMetastatic Hepatic Cancer / Nausea / Vomiting1
3CompletedTreatmentCessation, Smoking / Schizophrenic Disorders1
3Not Yet RecruitingSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV) / Colorectal Cancers1
4Active Not RecruitingTreatmentVomiting1
4CompletedTreatmentPain NOS1
Not AvailableCompletedBasic ScienceAnalgesia1
Not AvailableCompletedPreventionPost-Operative Nausea and Vomiting (PONV)2
Not AvailableNot Yet RecruitingTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
Not AvailableUnknown StatusSupportive CareNon-Hodgkin's Lymphoma (NHL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.33 mg/mLALOGPS
logP3.14ALOGPS
logP2.63ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)12.18ChemAxon
pKa (Strongest Basic)9.34ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area45.33 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity81.5 m3·mol-1ChemAxon
Polarizability31.35 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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 indolecarboxylic acids and derivatives. These are compounds containing a carboxylic acid group (or a derivative thereof) linked to an indole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolecarboxylic acids and derivatives
Direct Parent
Indolecarboxylic acids and derivatives
Alternative Parents
Tropane alkaloids / Indoles / Pyrrole carboxylic acids and derivatives / Benzenoids / Substituted pyrroles / Piperidines / N-alkylpyrrolidines / Vinylogous amides / Heteroaromatic compounds / Trialkylamines
show 8 more
Substituents
Indolecarboxylic acid derivative / Indole / Tropane alkaloid / Pyrrole-3-carboxylic acid or derivatives / Piperidine / Benzenoid / N-alkylpyrrolidine / Substituted pyrrole / Heteroaromatic compound / Vinylogous amide
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, azabicycloalkane, indolyl carboxylate ester (CHEBI:32269)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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

Drug created on October 20, 2016 14:40 / Updated on November 02, 2018 09:01