Identification
- Summary
Tropisetron is a 5HT-3 receptor antagonist used as an antiemetic in the treatment of chemotherapy-induced nausea and vomiting.
- Generic Name
- Tropisetron
- DrugBank Accession Number
- DB11699
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Tropisetron (DB11699)
- Weight
- Average: 284.3529
Monoisotopic: 284.152477894 - Chemical Formula
- C17H20N2O2
- Synonyms
- Tropisetron
Pharmacology
- Indication
For the prevention of nausea and vomiting induced by cytotoxic therapy and postoperative.
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- Contraindications & Blackbox Warnings
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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.
Target Actions Organism A5-hydroxytryptamine receptor 3A antagonistHumans - 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.
- Adverse Effects
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LD50: 265 mg/kg (Rat, oral).
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2D6 CYP2D6*1XN Not Available Normal allele duplicated. ADR Inferred Ultra-rapid drug metabolizer. Risk of toxicity, alternative drug recommended. Details Cytochrome P450 2D6 CYP2D6*2XN Not Available 2850C>T / 4180G>C … show all ADR Inferred Ultra-rapid drug metabolizer. Risk of toxicity, alternative drug recommended. Details
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 adverse effects can be increased when Tropisetron is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Tropisetron which could result in a higher serum level. Acebutolol Acebutolol may increase the arrhythmogenic activities of Tropisetron. Aceclofenac Aceclofenac may decrease the excretion rate of Tropisetron which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Tropisetron which could result in a higher serum level. Acenocoumarol The risk or severity of adverse effects can be increased when Tropisetron is combined with Acenocoumarol. Acetaminophen Acetaminophen may decrease the excretion rate of Tropisetron which could result in a higher serum level. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Tropisetron. Acetophenazine The risk or severity of adverse effects can be increased when Acetophenazine is combined with Tropisetron. Acetyldigitoxin Acetyldigitoxin may increase the arrhythmogenic activities of Tropisetron. 
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- Avoid alcohol.
Products
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Ingredient UNII CAS InChI Key Tropisetron Hydrochloride A19338Q2YO 105826-92-4 XIEGSJAEZIGKSA-LUNMCBQDSA-N Tropisetron Mesylate X2V6FDY03T 833482-77-2 FFTYLXTULVZQRZ-LUNMCBQDSA-N
Categories
- ATC Codes
- A04AA03 — Tropisetron
- Drug Categories
- Alimentary Tract and Metabolism
- Antiarrhythmic agents
- Antidepressive Agents
- Antiemetics
- Antiemetics and Antinauseants
- Autonomic Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Drugs that are Mainly Renally Excreted
- Gastrointestinal Agents
- Heterocyclic Compounds, Fused-Ring
- Indoles
- Neurotransmitter Agents
- Peripheral Nervous System Agents
- Serotonin 5-HT3 Receptor Antagonists
- Serotonin Agents
- Serotonin Receptor Antagonists
- Chemical TaxonomyProvided by Classyfire
- 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
- Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carboxylic acid derivative / Carboxylic acid ester / Heteroaromatic compound / Hydrocarbon derivative / Indole show 18 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tertiary amino compound, azabicycloalkane, indolyl carboxylate ester (CHEBI:32269)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6I819NIK1W
- CAS number
- 89565-68-4
- 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,3S,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
References
- General References
- External Links
- KEGG Compound
- C13666
- PubChem Compound
- 656665
- PubChem Substance
- 347828064
- ChemSpider
- 16736476
- BindingDB
- 50108392
- 27392
- ChEBI
- 32269
- ChEMBL
- CHEMBL56564
- ZINC
- ZINC000100019233
- PDBe Ligand
- TKT
- Wikipedia
- Tropisetron
- PDB Entries
- 2wnc / 5oaj / 6his
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Nausea / Vomiting 1 4 Completed Treatment Pain 1 4 Recruiting Other POCD - Postoperative Cognitive Dysfunction / Postoperative Delirium (POD) 1 4 Recruiting Supportive Care Chemotherapy-Induced Nausea and Vomiting 1 4 Recruiting Treatment Post Operative Nausea and Vomiting (PONV) 1 4 Unknown Status Prevention Emergence Delirium / Postoperative Delirium (POD) 1 4 Unknown Status Treatment Vomiting 1 3 Completed Supportive Care Chemotherapy-Induced Nausea and Vomiting / Colorectal Cancer 1 3 Completed Treatment Schizophrenia / Smoking, Cessation 1 3 Recruiting Prevention Antiemetics / Cervical Cancer / Chemotherapy-Induced Nausea and Vomiting / Nasopharyngeal Cancer / Radiation-Induced Nausea and Vomiting 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Injection Intravenous Injection, solution Oral Injection, solution Subcutaneous Injection, solution Intravenous 2 MG/2ML Solution Intravenous; Oral 5 mg/5ml Capsule Oral Injection, solution Intravenous 5 mg Capsule Oral 5 mg Injection, solution Intravenous 5 MG/5ML - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 1.33 mg/mL ALOGPS logP 3.14 ALOGPS logP 2.63 Chemaxon logS -2.3 ALOGPS pKa (Strongest Acidic) 12.18 Chemaxon pKa (Strongest Basic) 9.34 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 45.33 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 81.5 m3·mol-1 Chemaxon Polarizability 31.35 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- 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 at October 20, 2016 20:40 / Updated at May 27, 2021 02:57