tropisetron Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
serotonin receptor antagonists (5-HT3)	2775	89565-68-4

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: tropisetron navoban tropisetron hydrochloride tropisetron HCl	An indole derivative and 5-HT3 RECEPTOR antagonist that is used for the prevention of nausea and vomiting. Molecular weight: 284.36 Formula: C17H20N2O2 CLOGP: 2.88 LIPINSKI: 0 HAC: 4 HDO: 1 TPSA: 45.33 ALOGS: -2.33 ROTB: 3

Drug dosage:

Dose	Unit	Route
5	mg	O
5	mg	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	11 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	8 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.25 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	66 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	9.70 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	26 mL/min/kg	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	5.60 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Jan. 1, 1992	YEAR INTRODUCED

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Bone marrow failure	105.26	35.42	36	1268	30079	53317683
White blood cell count decreased	51.48	35.42	34	1270	124441	53223321
Neutrophil count decreased	40.46	35.42	21	1283	49077	53298685
Tongue neoplasm malignant stage unspecified	39.67	35.42	8	1296	842	53346920
Myelosuppression	35.80	35.42	13	1291	12815	53334947

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Bone marrow failure	42.43	33.37	20	977	30384	32482145
Myelosuppression	41.49	33.37	15	982	11661	32500868
Platelet count decreased	38.21	33.37	30	967	114561	32397968

Pharmacologic Action:

Source	Code	Description
ATC	A04AA03	ALIMENTARY TRACT AND METABOLISM ANTIEMETICS AND ANTINAUSEANTS ANTIEMETICS AND ANTINAUSEANTS Serotonin (5HT3) antagonists
MeSH PA	D000932	Antiemetics
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D005765	Gastrointestinal Agents
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D018373	Peripheral Nervous System Agents
MeSH PA	D058831	Serotonin 5-HT3 Receptor Antagonists
MeSH PA	D018490	Serotonin Agents
MeSH PA	D012702	Serotonin Antagonists
CHEBI has role	CHEBI:36335	trypanosomicidal agents
CHEBI has role	CHEBI:47958	muscarinic agonists
CHEBI has role	CHEBI:48279	5-hydroxytryptamine antagonists
CHEBI has role	CHEBI:50846	Biomodulator
CHEBI has role	CHEBI:50919	antiemetico
CHEBI has role	CHEBI:63726	neuroprotective agents
CHEBI has role	CHEBI:67079	antiinflammatory agents
CHEBI has role	CHEBI:68494	Type I programmed cell-death inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Chemotherapy-induced nausea and vomiting	indication	236084000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	12.91	acidic
pKa2	9.49	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
5-hydroxytryptamine receptor 3A	Ion channel	P46098	5HT3A_HUMAN	ANTAGONIST	Ki	8.80		IUPHAR	IUPHAR
Sodium-dependent serotonin transporter	Transporter	P31645	SC6A4_HUMAN		Ki	6.59		DRUG MATRIX
5-hydroxytryptamine receptor 1A	GPCR	P08908	5HT1A_HUMAN		Ki	8.28		CHEMBL
Muscarinic acetylcholine receptor M5	GPCR	P08912	ACM5_HUMAN		Ki	5.61		DRUG MATRIX
Glycine receptor subunit alpha-1	Ion channel	P23415	GLRA1_HUMAN	ANTAGONIST	Ki	4.10		IUPHAR
Glycine receptor subunit alpha-2	Ion channel	P23416	GLRA2_HUMAN	ANTAGONIST	Ki	4.90		IUPHAR
5-hydroxytryptamine receptor 4	GPCR	Q13639	5HT4R_HUMAN		Ki	6.85		WOMBAT-PK
Neuronal acetylcholine receptor subunit alpha-7	Ion channel	P36544	ACHA7_HUMAN		Ki	8.16		CHEMBL
Glycine receptor subunit beta	Ion channel	P48167	GLRB_HUMAN	ANTAGONIST	Ki	5.30		IUPHAR
Neuronal acetylcholine receptor; alpha4/beta2	Ion channel	P17787 P43681	ACHB2_HUMAN ACHA4_HUMAN		Ki	4.26		CHEMBL
Acetylcholine receptor; alpha1/beta1/delta/gamma	Ion channel	P02708 P07510 P11230 Q07001	ACHA_HUMAN ACHG_HUMAN ACHB_HUMAN ACHD_HUMAN		Ki	4.57		CHEMBL
5-hydroxytryptamine receptor 3B	Ion channel	O95264	5HT3B_HUMAN		Ki	8.80		CHEMBL
Neuronal acetylcholine receptor subunit alpha-3	Ion channel	P32297	ACHA3_HUMAN		Ki	4.80		CHEMBL
Neuronal acetylcholine receptor subunit alpha-7	Ion channel		ACHA7_RAT		EC50	8		CHEMBL
5-hydroxytryptamine receptor 4	GPCR		5HT4R_RAT		Ki	7.20		CHEMBL
Neuronal acetylcholine receptor subunit alpha-7	Ion channel		ACHA7_MOUSE		Ki	8.16		CHEMBL
5-hydroxytryptamine receptor 3A	Ion channel		5HT3A_CAVPO		Kd	7.52		CHEMBL
Serotonin 3 (5-HT3) receptor	Ion channel		5HT3A_RAT 5HT3B_RAT		Ki	8.89		CHEMBL
Serotonin 3 receptor (5HT3)	Ion channel		5HT3A_MOUSE 5HT3B_MOUSE		Ki	8.42		CHEMBL
5-hydroxytryptamine receptor 4	GPCR		5HT4R_CAVPO		Ki	6.90		CHEMBL
5-hydroxytryptamine receptor 4	GPCR		5HT4R_MOUSE	ANTAGONIST	Ki	7.10		IUPHAR

External reference:

ID	Source
D02041	KEGG_DRUG
105826-92-4	SECONDARY_CAS_RN
C0063322	UMLSCUI
CHEBI:32269	CHEBI
TKT	PDB_CHEM_ID
CHEMBL56564	ChEMBL_ID
DB11699	DRUGBANK_ID
D000077526	MESH_DESCRIPTOR_UI
656665	PUBCHEM_CID
260	IUPHAR_LIGAND_ID
6535	INN_ID
6I819NIK1W	UNII
235997	RXNORM
004472	NDDF
004473	NDDF
322201005	SNOMEDCT_US
395917006	SNOMEDCT_US
426339000	SNOMEDCT_US

Pharmaceutical products:

None