General
Preferred name
ONDANSETRON
Synonyms
ONDANSETRON HYDROCHLORIDE ()
Demorem ()
Setofilm ()
Ondemet ()
Ondansetron (hydrochloride) ()
GR 38032 (hydrochloride) ()
SN 307 (hydrochloride) ()
NSC 665799 ()
SN 307 ()
GR 38032 ()
Ondansetron Hydrochloride Dihydrate ()
Ondansetron HCl ()
Ondansetron (Zofran) ()
Ondansetron (hydrochloride dihydrate) ()
GR 38032 (hydrochloride dihydrate) ()
SN 307 (hydrochloride dihydrate) ()
Ondemet, Emeset, Emetron,GR 38032F,SN 307 ()
GR-38032F ()
Zofran ()
Zofran Odt ()
Desmethylondansetron ()
EUR-1025 ()
GR-38032 ()
Zuplenz ()
A04AA01 ()
NSC-757870 ()
ondansetron ()
GR 38032F ()
NSC-665799 ()
Zophren ()
Odansetron hydrochloride ()
Ondansetron hydrochloride hydrate ()
Ondansetron (as hydrochloride) ()
Zofran preservative free ()
Ondansetron hydrochloride preservative free ()
Ondansetron monohydrochloride ()
Ondansetron hydrochloride dihydrate ()
SN-307 ()
Ondansetron (hydrochloride hydrate) ()
Ondansetron (hydrochloride) (CRM) ()
Ondansetron-13C-d3 ()
P&D ID
PD002938
CAS
99614-02-5
103639-04-9
99614-01-4
110204-46-1
108303-49-7
2699607-85-5
Tags
natural product
drug
available
Approved by
PMDA
FDA
First approval
1991
Drug Status
approved
withdrawn
Drug indication
Alcohol dependence
Chemotherapy-induced nausea
Anti-Emetic
Anti-Anxiety Agent
Antischizophrenic
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA Ondansetron is a selective antagonist of the serotonin receptor subtype, 5-HT3 [F3178, F3181, F3184]. Cytotoxic chemotherapy and radiotherapy are associated with the release of serotonin (5-HT) from enterochromaffin cells of the small intestine, presumably initiating a vomiting reflex through stimulation of 5-HT3 receptors located on vagal afferents [F3178, F3181, F3184]. Ondansetron may block the initiation of this reflex. Activation of vagal afferents may also cause a central release of serotonin from the chemoreceptor trigger zone of the area postrema, located on the floor of the fourth ventricle [F3178, F3181, F3184]. Thus, the antiemetic effect of ondansetron is probably due to the selective antagonism of 5-HT3 receptors on neurons located in either the peripheral or central nervous systems, or both [F3178, F3181, F3184]. Although the mechanisms of action of ondansetron in treating postoperative nausea and vomiting and cytotoxic induced nausea and vomiting may share similar pathways, the role of ondansetron in opiate-induced emesis has not yet been formally established [F3181, F3184].
ROE Following oral or IV administration, ondansetron is extensively metabolised and excreted in the urine and faeces [F3181, F3184].
HALF-LIFE The half-life of ondansetron after either an 8 mg oral dose or intravenous dose was approximately 3-4 hours and could be extended to 6-8 hours in the elderly [F3181, F3184].
ABSORPTION Ondansetron is absorbed from the gastrointestinal tract and undergoes some limited first-pass metabolism [F3178]. Mean bioavailability in healthy subjects, following administration of a single 8-mg tablet, was recorded as being approximately 56% to 60% [F3178, F3181, F3184]. Bioavailability is also slightly enhanced by the presence of food [F3178]. Ondansetron systemic exposure does not increase proportionately to dose [F3178]. The AUC from a 16-mg tablet was 24% greater than predicted from an 8-mg tablet dose [F3178]. This may reflect some reduction of first-pass metabolism at higher oral doses [F3178].
TOXICITY At present, there is little information concerning overdosage with ondansetron [F3178, F3181, F3184]. Nevertheless, there have been certain cases of somewhat idiosyncratic adverse effects associated with particular dosages of ondansetron used [F3178, F3181, F3184].; ; “Sudden blindness” (amaurosis) of 2 to 3 minutes duration plus severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as a single dose [F3178, F3181, F3184]. Hypotension (and faintness) occurred in another patient that took 48 mg of oral ondansetron [F3178, F3181, F3184]. Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed [F3178, F3181, F3184]. Neuromuscular abnormalities, autonomic instability, somnolence, and a brief generalized tonic-clonic seizure (which resolved after a dose of benzodiazepine) were observed in a 12-month-old infant who ingested seven or eight 8-mg ondansetron tablets (approximately forty times the recommended 0.1-0.15 mg/kg dose for a pediatric patient) [F3178, F3181, F3184]. In all instances, however, the events resolved completely [F3178, F3181, F3184].; ; The safety of ondansetron for use in human pregnancy has not been established [F3181, F3184]. Ondansetron is not teratogenic in animals [F3181, F3184]. However, as animal studies are not always predictive of human response, the use of ondansetron in pregnancy is not recommended [F3181, F3184].; ; Ondansetron is excreted in the milk of lactating rats [F3181, F3184]. It is not known if it is excreted in human milk, however, nursing is not recommended during treatment with ondansetron [F3181, F3184].; ; Insufficient information is available to provide dosage recommendations for children 3 years of age or younger [F3181, F3184].
ABSORPTION Ondansetron is absorbed from the gastrointestinal tract and undergoes some limited first-pass metabolism [F3178]. Mean bioavailability in healthy subjects, following administration of a single 8-mg tablet, was recorded as being approximately 56% to 60% [F3178, F3181, F3184]. Bioavailability is also slightly enhanced by the presence of food [F3178].; ; Ondansetron systemic exposure does not increase proportionately to dose [F3178]. The AUC from a 16-mg tablet was 24% greater than predicted from an 8-mg tablet dose [F3178]. This may reflect some reduction of first-pass metabolism at higher oral doses [F3178].
DESCRIPTION The approved drug ondansetron is a racemic mixture of two enantiomers. The structure shown here does not specify stereochemistry and represents the mixture. (GtoPdb)
INDICATION In the adult patient population: i) orally administered ondansetron tablets and orally disintegrating tablets (ODT) are indicated for: - the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, including high dose (ie. greater than or equal to 50 mg/m2) cisplatin therapy, and radiotherapy, and - the prevention and treatment of postoperative nausea and vomiting ii) intravenously administered ondansetron injection formulations are indicated for: - the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, including high dose (ie. greater than or equal to 50 mg/m2) cisplatin therapy, and - the prevention and treatment of postoperative nausea and vomiting In the pediatric (4-18 years of age) patient population: i) ondansetron was effective and well tolerated when given to children 4-12 years of age for the treatment of post-chemotherapy induced nausea and vomiting, ii) ondansetron tablets, ondansetron ODT, ondansetron injection are not indicated for the treatment of children 3 years of age or younger, iii) ondansetron tablets, ondansetron ODT, ondansetron injection are not indicated for use in any age group of the pediatric population for the treatment of post-radiotherapy induced nausea and vomiting, and iV) ondansetron tablets, ondansetron ODT, ondansetron injection are not indicated for use in any age group of the pediatric population for the treatment of postoperative nausea and vomiting In the geriatric (>65 years of age) patient population: i) efficacy and tolerance of ondansetron were similar to that observed in younger adults for the treatment of post-chemotherapy and radiotherapy-induced nausea and vomiting, and ii) clinical experience in the use of ondansetron in the prevention and treatment of postoperative nausea and vomiting is limited and is not indicated for use in the geriatric patient population
TOXICITY At present, there is little information concerning overdosage with ondansetron [F3178, F3181, F3184]. Nevertheless, there have been certain cases of somewhat idiosyncratic adverse effects associated with particular dosages of ondansetron used [F3178, F3181, F3184]. “Sudden blindness” (amaurosis) of 2 to 3 minutes duration plus severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as a single dose [F3178, F3181, F3184]. Hypotension (and faintness) occurred in another patient that took 48 mg of oral ondansetron [F3178, F3181, F3184]. Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed [F3178, F3181, F3184]. Neuromuscular abnormalities, autonomic instability, somnolence, and a brief generalized tonic-clonic seizure (which resolved after a dose of benzodiazepine) were observed in a 12-month-old infant who ingested seven or eight 8-mg ondansetron tablets (approximately forty times the recommended 0.1-0.15 mg/kg dose for a pediatric patient) [F3178, F3181, F3184]. In all instances, however, the events resolved completely [F3178, F3181, F3184]. The safety of ondansetron for use in human pregnancy has not been established [F3181, F3184]. Ondansetron is not teratogenic in animals [F3181, F3184]. However, as animal studies are not always predictive of human response, the use of ondansetron in pregnancy is not recommended [F3181, F3184]. Ondansetron is excreted in the milk of lactating rats [F3181, F3184]. It is not known if it is excreted in human milk, however, nursing is not recommended during treatment with ondansetron [F3181, F3184]. Insufficient information is available to provide dosage recommendations for children 3 years of age or younger [F3181, F3184].
METABOLISM In vitro metabolism studies have shown that ondansetron is a substrate for human hepatic cytochrome P450 enzymes, including CYP1A2, CYP2D6 and CYP3A4 [F3178, F3181, F3184]. In terms of overall ondansetron turnover, CYP3A4 played the predominant role [F3178, F3181, F3184]. Because of the multiplicity of metabolic enzymes capable of metabolizing ondansetron, it is likely that inhibition or loss of one enzyme (e.g. CYP2D6 enzyme deficiency) will be compensated by others and may result in little change in overall rates of ondansetron clearance [F3178, F3181, F3184]. Following oral or IV administration, ondansetron is extensively metabolised and excreted in the urine and faeces [F3178, F3181, F3184]. In humans, less than 10% of the dose is excreted unchanged in the urine [F3178, F3181, F3184]. The major urinary metabolites are glucuronide conjugates (45%), sulphate conjugates (20%) and hydroxylation products (10%) [F3178, F3181, F3184]. The primary metabolic pathway is subsequently hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation [F3178, F3181, F3184]. Although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of ondansetron [F3178, F3181, F3184].
MOA Ondansetron is a selective antagonist of the serotonin receptor subtype, 5-HT3 [F3178, F3181, F3184].; ; Cytotoxic chemotherapy and radiotherapy are associated with the release of serotonin (5-HT) from enterochromaffin cells of the small intestine, presumably initiating a vomiting reflex through stimulation of 5-HT3 receptors located on vagal afferents [F3178, F3181, F3184]. Ondansetron may block the initiation of this reflex. Activation of vagal afferents may also cause a central release of serotonin from the chemoreceptor trigger zone of the area postrema, located on the floor of the fourth ventricle [F3178, F3181, F3184]. Thus, the antiemetic effect of ondansetron is probably due to the selective antagonism of 5-HT3 receptors on neurons located in either the peripheral or central nervous systems, or both [F3178, F3181, F3184].; ; Although the mechanisms of action of ondansetron in treating postoperative nausea and vomiting and cytotoxic induced nausea and vomiting may share similar pathways, the role of ondansetron in opiate-induced emesis has not yet been formally established [F3181, F3184].
INDICATION In the adult patient population:; i) orally administered ondansetron tablets and orally disintegrating tablets (ODT) are indicated for:; - the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, including high dose (ie. greater than or equal to 50 mg/m2) cisplatin therapy, and radiotherapy, and; - the prevention and treatment of postoperative nausea and vomiting; ; ii) intravenously administered ondansetron injection formulations are indicated for:; - the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, including high dose (ie. greater than or equal to 50 mg/m2) cisplatin therapy, and; - the prevention and treatment of postoperative nausea and vomiting; ; In the pediatric (4-18 years of age) patient population:; i) ondansetron was effective and well tolerated when given to children 4-12 years of age for the treatment of post-chemotherapy induced nausea and vomiting,; ii) ondansetron tablets, ondansetron ODT, ondansetron injection are not indicated for the treatment of children 3 years of age or younger,; iii) ondansetron tablets, ondansetron ODT, ondansetron injection are not indicated for use in any age group of the pediatric population for the treatment of post-radiotherapy induced nausea and vomiting, and; iV) ondansetron tablets, ondansetron ODT, ondansetron injection are not indicated for use in any age group of the pediatric population for the treatment of postoperative nausea and vomiting; ; In the geriatric (>65 years of age) patient population:; i) efficacy and tolerance of ondansetron were similar to that observed in younger adults for the treatment of post-chemotherapy and radiotherapy-induced nausea and vomiting, and; ii) clinical experience in the use of ondansetron in the prevention and treatment of postoperative nausea and vomiting is limited and is not indicated for use in the geriatric patient population
METABOLISM In vitro metabolism studies have shown that ondansetron is a substrate for human hepatic cytochrome P450 enzymes, including CYP1A2, CYP2D6 and CYP3A4 [F3178, F3181, F3184]. In terms of overall ondansetron turnover, CYP3A4 played the predominant role [F3178, F3181, F3184]. Because of the multiplicity of metabolic enzymes capable of metabolizing ondansetron, it is likely that inhibition or loss of one enzyme (e.g. CYP2D6 enzyme deficiency) will be compensated by others and may result in little change in overall rates of ondansetron clearance [F3178, F3181, F3184].; ; Following oral or IV administration, ondansetron is extensively metabolised and excreted in the urine and faeces [F3178, F3181, F3184]. In humans, less than 10% of the dose is excreted unchanged in the urine [F3178, F3181, F3184]. The major urinary metabolites are glucuronide conjugates (45%), sulphate conjugates (20%) and hydroxylation products (10%) [F3178, F3181, F3184]. The primary metabolic pathway is subsequently hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation [F3178, F3181, F3184]. Although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of ondansetron [F3178, F3181, F3184].
DESCRIPTION Ondansetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic. (BOC Sciences Bioactive Compounds)
DESCRIPTION Ondansetron hydrochloride dihydrate is a specific and competitive antagonist of serotonin 5-HT3 receptor (Ki = 0.77 nM) with anxiolytic and neuroleptic activities. It can be used for the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, such as cisplatin. (BOC Sciences Bioactive Compounds)
DESCRIPTION GluN2B-selective NMDA antagonist; also sigma agonist (Tocris Bioactive Compound Library)
Cell lines
0
Organisms
2
Compound Sets
34
AdooQ Bioactive Compound Library
A11701
BOC Sciences Bioactive Compounds
ondansetron-hydrochloride-dihydrate-cas-103639-04-9-item-303235
ondansetron-cas-99614-02-5-item-84-80575
Cayman Chemical Bioactives
21710
14999
25754
ChEMBL Approved Drugs
CHEMBL3186492
CHEMBL46
ChEMBL Drugs
CHEMBL3186492
CHEMBL46
Concise Guide to Pharmacology 2017/18
2290
Concise Guide to Pharmacology 2019/20
2290
Concise Guide to Pharmacology 2021/22
2290
Concise Guide to Pharmacology 2023/24
2290
DrugBank
DB00904
DrugBank Approved Drugs
DB00904
DrugCentral
1992
DrugCentral Approved Drugs
1992
DrugMAP
DMOTQ1I
DrugMAP Approved Drugs
DMOTQ1I
DrugMatrix
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS102158
Guide to Pharmacology
2290
Ki Database
Ondansetron HCl
ONDANSETRON
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL46
Mcule NIBR MoA Box Subset
MCULE-9438746800
MedChem Express Bioactive Compound Library
HY-B0002A
HY-B0002B
NCATS Inxight Approved Drugs
4AF302ESOS
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Other bioactive compounds
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Ondansetron-hydrochloride
ondansetron-hcl
TargetMol Bioactive Compound Library
T1478
The Spectrum Collection
Tocris Bioactive Compound Library
2891
External IDs
85
Properties
(calculated by RDKit )
Molecular Weight
293.15
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
0
Rotatable Bonds
2
Ring Count
4
Aromatic Ring Count
3
cLogP
3.13
TPSA
39.82
Fraction CSP3
0.33
Chiral centers
1.0
Largest ring
6.0
QED
0.73
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
GPCR/G protein
Neuroscience
Neuronal Signaling
Target
5-HT3
5-HT Receptor
Primary Target
5-HT3 Receptors
MOA
5-HT Receptor antagonist
Antagonist
5-HT3 receptor antagonist
Member status
member
Therapeutic Class
Antiemetics
Solubility
DMSO Solubility: 73 mg/mL warmed (199.53 mM)
Source data