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][[email protected]]12CC[[email protected]]([H])(C[[email protected]@]([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.

Structured Indications
Not Available
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
DrugInteractionDrug group
AlmotriptanTropisetron may increase the serotonergic activities of Almotriptan.Approved, Investigational
AmitriptylineTropisetron may increase the serotonergic activities of Amitriptyline.Approved
AmoxapineTropisetron may increase the serotonergic activities of Amoxapine.Approved
ApomorphineTropisetron may increase the hypotensive activities of Apomorphine.Approved, Investigational
BromocriptineTropisetron may increase the serotonergic activities of Bromocriptine.Approved, Investigational
BuspironeTropisetron may increase the serotonergic activities of Buspirone.Approved, Investigational
CabergolineTropisetron may increase the serotonergic activities of Cabergoline.Approved
CitalopramTropisetron may increase the serotonergic activities of Citalopram.Approved
ClomipramineTropisetron may increase the serotonergic activities of Clomipramine.Approved, Vet Approved
CyclobenzaprineTropisetron may increase the serotonergic activities of Cyclobenzaprine.Approved
DesipramineTropisetron may increase the serotonergic activities of Desipramine.Approved
DesvenlafaxineTropisetron may increase the serotonergic activities of Desvenlafaxine.Approved
DextromethorphanTropisetron may increase the serotonergic activities of Dextromethorphan.Approved
DihydroergotamineTropisetron may increase the serotonergic activities of Dihydroergotamine.Approved
DoxepinTropisetron may increase the serotonergic activities of Doxepin.Approved
DuloxetineTropisetron may increase the serotonergic activities of Duloxetine.Approved
EletriptanTropisetron may increase the serotonergic activities of Eletriptan.Approved, Investigational
Ergoloid mesylateTropisetron may increase the serotonergic activities of Ergoloid mesylate.Approved
ErgonovineTropisetron may increase the serotonergic activities of Ergonovine.Approved
ErgotamineTropisetron may increase the serotonergic activities of Ergotamine.Approved
EscitalopramTropisetron may increase the serotonergic activities of Escitalopram.Approved, Investigational
FentanylTropisetron may increase the serotonergic activities of Fentanyl.Approved, Illicit, Investigational, Vet Approved
FluoxetineTropisetron may increase the serotonergic activities of Fluoxetine.Approved, Vet Approved
FluvoxamineTropisetron may increase the serotonergic activities of Fluvoxamine.Approved, Investigational
FrovatriptanTropisetron may increase the serotonergic activities of Frovatriptan.Approved, Investigational
ImipramineTropisetron may increase the serotonergic activities of Imipramine.Approved
IsocarboxazidTropisetron may increase the serotonergic activities of Isocarboxazid.Approved
LevomilnacipranTropisetron may increase the serotonergic activities of Levomilnacipran.Approved
LinezolidTropisetron may increase the serotonergic activities of Linezolid.Approved, Investigational
LithiumTropisetron may increase the serotonergic activities of Lithium.Approved
LorcaserinTropisetron may increase the serotonergic activities of Lorcaserin.Approved
MaprotilineTropisetron may increase the serotonergic activities of Maprotiline.Approved
MethadoneTropisetron may increase the serotonergic activities of Methadone.Approved
MilnacipranTropisetron may increase the serotonergic activities of Milnacipran.Approved
MirtazapineTropisetron may increase the serotonergic activities of Mirtazapine.Approved
MoclobemideTropisetron may increase the serotonergic activities of Moclobemide.Approved
NaratriptanTropisetron may increase the serotonergic activities of Naratriptan.Approved, Investigational
NefazodoneTropisetron may increase the serotonergic activities of Nefazodone.Approved, Withdrawn
NortriptylineTropisetron may increase the serotonergic activities of Nortriptyline.Approved
ParoxetineTropisetron may increase the serotonergic activities of Paroxetine.Approved, Investigational
PethidineTropisetron may increase the serotonergic activities of Pethidine.Approved
PhenelzineTropisetron may increase the serotonergic activities of Phenelzine.Approved
ProcarbazineTropisetron may increase the serotonergic activities of Procarbazine.Approved
PromethazineTropisetron may increase the serotonergic activities of Promethazine.Approved
ProtriptylineTropisetron may increase the serotonergic activities of Protriptyline.Approved
RasagilineTropisetron may increase the serotonergic activities of Rasagiline.Approved
RizatriptanTropisetron may increase the serotonergic activities of Rizatriptan.Approved
SelegilineTropisetron may increase the serotonergic activities of Selegiline.Approved, Investigational, Vet Approved
SertralineTropisetron may increase the serotonergic activities of Sertraline.Approved
SumatriptanTropisetron may increase the serotonergic activities of Sumatriptan.Approved, Investigational
TapentadolTropisetron may decrease the analgesic activities of Tapentadol.Approved
Tedizolid PhosphateTropisetron may increase the serotonergic activities of Tedizolid Phosphate.Approved
TramadolTropisetron may decrease the analgesic activities of Tramadol.Approved, Investigational
TranylcypromineTropisetron may increase the serotonergic activities of Tranylcypromine.Approved
TrazodoneTropisetron may increase the serotonergic activities of Trazodone.Approved, Investigational
TrimipramineTropisetron may increase the serotonergic activities of Trimipramine.Approved
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Tropisetron.Approved
VenlafaxineTropisetron may increase the serotonergic activities of Venlafaxine.Approved
VilazodoneTropisetron may increase the serotonergic activities of Vilazodone.Approved
VortioxetineTropisetron may increase the serotonergic activities of Vortioxetine.Approved
ZolmitriptanTropisetron may increase the serotonergic activities of Zolmitriptan.Approved, Investigational
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
ATC Codes
A04AA03 — Tropisetron
PDB Entries
2wnc

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedSupportive CareNausea and Vomiting / Unspecified Adult Solid Tumor, Protocol Specific1
2CompletedTreatmentChronic Diseases / Pain1
2Unknown StatusPreventionHepatic cancer metastatic / Nausea / Vomiting1
3CompletedTreatmentCessation, Smoking / Schizophrenic Disorders1
3Not Yet RecruitingSupportive CareColorectal Cancers / Prophylaxis of acute chemotherapy induced nausea and vomiting1
4Active Not RecruitingTreatmentVomiting1
4CompletedTreatmentPain1
Not AvailableCompletedBasic ScienceAnalgesia1
Not AvailableCompletedPreventionProphylaxis against postoperative nausea and vomiting1
Not AvailableNot Yet RecruitingTreatmentProphylaxis of acute chemotherapy induced nausea and vomiting1
Not AvailableRecruitingPreventionProphylaxis against postoperative nausea and vomiting1
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 December 01, 2017 17:30