Tropisetron

Summary

Tropisetron (CHEMBL56564) is an approved small-molecule serotonergic antagonist (ATC A04AA03) targeting GLRA1, GLRA2, and GLRB; indicated across 3 conditions.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A04AA03
• Targets: 4 (GLRA1, GLRA2, GLRB…)
• Indications: 3 conditions
• Clinical trials: 16
• Chemistry: 284.35 Da · C17H20N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL56564
Name	Tropisetron
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	656665
ChEBI	CHEBI:32269
ATC	A04AA03
Molecular formula	C17H20N2O2
Molecular weight	284.35
InChIKey	ZNRGQMMCGHDTEI-FUNVUKJBSA-N

SMILES: CN1[C@@H]2CC[C@H]1CC(C2)OC(=O)C3=CNC4=CC=CC=C43

IUPAC name: [(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 1H-indole-3-carboxylate

ChEBI definition: An indolyl carboxylate ester obtained by formal condensation of the carboxy group of indole-3-carboxylic acid with the hydroxy group of tropine.

Pharmacological roles (ChEBI): serotonergic antagonist, antiemetic, nicotinic acetylcholine receptor agonist, trypanocidal drug, immunomodulator, neuroprotective agent, apoptosis inhibitor, anti-inflammatory agent.

Also known as: Navoban, Novaban, NSC-759842, SDZ-ICS-930, Tropisetron, Tropisetron (as hydrochloride), Tropisetron hcl, Tropisetron hydrochloride, Tropisetron monohydrochloride, tropisetron, SID11111839, SID26755041

Parent form; salt/anhydrous children: CHEMBL2130744, CHEMBL3348564

Patent coverage: 4,603 distinct patent families (19,312 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 19,302 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
	5-HT3A	Antagonist	8.8
GLRA1	glycine receptor α1 subunit	Antagonist	4.1	0.3%	P23415
GLRA2	glycine receptor α2 subunit	Antagonist	4.9	0.4%	P23416
GLRB	glycine receptor β subunit	Antagonist	5.3	0.2%	P48167
	Glycine Receptor (All subtypes)	Antagonist	4.1
HTR4	5-HT4 receptor	Antagonist	7.1	0%	Q13639

Broader ChEMBL bioactivity targets: 31 (assay-derived). Sample: Microtubule-associated protein tau, 5-hydroxytryptamine receptor 2B, 5-hydroxytryptamine receptor 4, Neuronal acetylcholine receptor subunit alpha-4, 5-hydroxytryptamine receptor 3A, Acetylcholine receptor; alpha1/beta1/delta/gamma, Neuronal acetylcholine receptor; alpha4/beta2, Neuronal acetylcholine receptor; alpha3/beta4, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor.

Bioactivity

ChEMBL activities: 61 potent at pChembl ≥ 5 of 71 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR3E	10.6	Kd	0.03	nM	CHEMBL_ACT_919037
HTR3E	10.2	Kd	0.06	nM	CHEMBL_ACT_779545
HTR3E	10.2	Kd	0.06	nM	CHEMBL_ACT_919036
P35563	9.22	Ki	0.6	nM	CHEMBL_ACT_779550
P35563	8.9	IC50	1.26	nM	CHEMBL_ACT_1067432
P35563	8.89	Ki	1.28	nM	CHEMBL_ACT_337482
P35563	8.89	Ki	1.29	nM	CHEMBL_ACT_337483
P35563	8.89	Ki	1.28	nM	CHEMBL_ACT_820644
P35563	8.85	IC50	1.4	nM	CHEMBL_ACT_750134
P35563	8.81	Ki	1.55	nM	CHEMBL_ACT_450351
P35563	8.8	Ki	1.57	nM	CHEMBL_ACT_1002811
P35563	8.8	Ki	1.58	nM	CHEMBL_ACT_657669
P35563	8.77	Ki	1.71	nM	CHEMBL_ACT_80556
P35563	8.7	Ki	2	nM	CHEMBL_ACT_409260
P35563	8.64	IC50	2.3	nM	CHEMBL_ACT_856100
HTR3A	8.57	Ki	2.7	nM	CHEMBL_ACT_387620
HTR3A	8.57	Ki	2.7	nM	CHEMBL_ACT_633646
P35563	8.57	Ki	2.7	nM	CHEMBL_ACT_675341
HTR3A	8.55	Ki	2.82	nM	CHEMBL_ACT_2411226
P35563	8.51	IC50	3.1	nM	CHEMBL_ACT_750132
P35563	8.5	Ki	3.16	nM	CHEMBL_ACT_779549
P35563	8.49	Ki	3.2	nM	CHEMBL_ACT_646970
P23979	8.42	Ki	3.8	nM	CHEMBL_ACT_800225
HTR3A	8.28	Ki	5.3	nM	CHEMBL_ACT_12053427
HTR1A	8.28	Ki	5.3	nM	CHEMBL_ACT_1613681
HTR3E	8.28	Ki	5.3	nM	CHEMBL_ACT_393619
CHRNA7	8.16	Ki	6.9	nM	CHEMBL_ACT_12053429
CHRNA7	8.16	Ki	6.9	nM	CHEMBL_ACT_1613680
P49582	8.16	Ki	6.9	nM	CHEMBL_ACT_393618
HTR3A	8.1	AC50	8	nM	CHEMBL_ACT_25149744

Target pathways

Aggregated over 4 target gene(s): GLRA1, GLRA2, GLRB, HTR4.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Neurotransmitter receptors and postsynaptic signal transmission	3	GLRA1, GLRA2, GLRB
Signal Transduction	1	HTR4
Signaling by GPCR	1	HTR4
Class A/1 (Rhodopsin-like receptors)	1	HTR4
Amine ligand-binding receptors	1	HTR4
GPCR downstream signalling	1	HTR4
Serotonin receptors	1	HTR4
G alpha (s) signalling events	1	HTR4
GPCR ligand binding	1	HTR4

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	3
chloride transport	3
neuropeptide signaling pathway	3
chloride transmembrane transport	3
chemical synaptic transmission	3
monoatomic ion transmembrane transport	3
excitatory postsynaptic potential	3
startle response	2
acrosome reaction	2
visual perception	2
adult walking behavior	2
regulation of membrane potential	2
synaptic transmission, glycinergic	2
righting reflex	2
cellular response to amino acid stimulus	2

Indications & clinical

Indications

3 indications (2 at ChEMBL trial phase 4).

The 3 indication records carry no mapped disease name (EFO/MeSH-only); none shown.

Clinical trials

Total trials: 16.

Phase distribution

Phase	Trials
PHASE4	5
PHASE3	4
Not specified	4
PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00487110	PHASE4	COMPLETED	Clinical Confirmation of a Pharmacodynamic Interaction Between Tropisetron and Paracetamol
NCT02576327	PHASE4	UNKNOWN	A Study Evaluating the Efficacy and Safety of Aprepitant in Autologous Hematopoietic Stem Cell Transplantation
NCT04027751	PHASE4	UNKNOWN	The Efficacy and Safety of Tropisetron in Preventing Emergence Delirium
NCT04195204	PHASE4	UNKNOWN	A Pilot Trial Evaluating the Effect of Tropisetron on Postoperative Cognitive Dysfunction After Cardiac Surgery
NCT05533281	PHASE4	COMPLETED	Efficacy of Three Antiemetics in Preventing Nausea and Vomiting
NCT07413809	PHASE3	RECRUITING	Prevention of Delayed CINV After Autologous Transplant: Olanzapine-Containing Regimen vs. Dexamethasone-Containing Regimen
NCT00435370	PHASE3	COMPLETED	Effectiveness of Tropisetron Plus Risperidone for Improving Cognitive and Perceptual Disturbances in Schizophrenia
NCT02909478	PHASE3	COMPLETED	Aprepitant Without Steroid in Preventing Chemotherapy-induced Nausea and Vomiting in Patients With Colorectal Cancer
NCT05564286	PHASE3	COMPLETED	Triple Antiemetic Regimen for Chemoradiotherapy in Cervical Cancer or Nasopharyngeal Cancer
NCT00003817	PHASE2	COMPLETED	Acupressure and Acustimulation Wrist Bands for the Prevention of Nausea and Vomiting Caused by Chemotherapy
NCT00889499	PHASE2	COMPLETED	Modulation of Central Hypersensitivity in Chronic Musculoskeletal Pain by Intravenous Tropisetron
NCT01895010	PHASE2	UNKNOWN	Acupoint Electric Stimulation Combined With Tropisetron in Preventing and Treating Nausea and Vomiting After TACE
NCT07554040	Not specified	NOT_YET_RECRUITING	Amisulpride for the Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Surgery
NCT00970450	Not specified	COMPLETED	The Central Analgesic Effects of Paracetamol on Serotonergic Pathways
NCT02096835	Not specified	COMPLETED	Transcutaneous Electrical Acupoint Stimulation of P6 to Prevent Postoperation Nausea and Vomiting
NCT02625181	Not specified	COMPLETED	Real-time Decision Support for Postoperative Nausea and Vomiting (PONV) Prophylaxis

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for tropisetron and CYP2D6	CPIC	CYP2D6		yes

PharmGKB also curates 2 clinical and 6 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

35 molecules share ≥1 primary target. Top 35 by shared-target count:

Molecule	Source	Status	Shared targets
Serotonin	ChEMBL + PubChem	Phase 3 (approved)	GLRA1, HTR4
ADAPALENE	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
CANNABIDIOL	ChEMBL + PubChem	Phase 4 (approved)	GLRA2
CHOLECALCIFEROL	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
CINACALCET	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
DRONABINOL	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
DUTASTERIDE	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
GLYCINE	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR4
MEFLOQUINE	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
PIMOZIDE	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
PRUCALOPRIDE	ChEMBL + PubChem	Phase 4 (approved)	HTR4
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
RISPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
SULINDAC	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
TEGASEROD	ChEMBL + PubChem	Phase 4 (approved)	HTR4
TELMISARTAN	ChEMBL + PubChem	Phase 4 (approved)	GLRA1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	GLRA1
CISAPRIDE	ChEMBL	Phase 4 (approved)	HTR4
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	GLRA1
METOCLOPRAMIDE	ChEMBL	Phase 4 (approved)	HTR4
FELCISETRAG	ChEMBL	Phase 2	HTR4
FRUCTOSE	ChEMBL	Phase 2	GLRA1
LITOXETINE	ChEMBL	Phase 2	HTR4
MEBUFOTENIN	ChEMBL	Phase 2	HTR4
PIBOSEROD	ChEMBL	Phase 2	HTR4
PRX-03140	ChEMBL	Phase 2	HTR4
VELUSETRAG	ChEMBL	Phase 2	HTR4
.gamma.-aminobutyric acid	PubChem	Approved	GLRA1
Acetylcholine	PubChem	Approved	GLRA1
Cyproheptadine	PubChem	Approved	HTR4
Donepezil	PubChem	Approved	HTR4
Haloperidol	PubChem	Approved	HTR4
Propofol	PubChem	Approved	GLRA1
Zuranolone	PubChem	Approved	GLRA1