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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H24N2O
Molecular Weight 296.4074
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PALONOSETRON

SMILES

C1Cc2cccc3c2[C@]([H])(C1)CN([C@]4([H])CN5CCC4CC5)C3=O

InChI

InChIKey=CPZBLNMUGSZIPR-NVXWUHKLSA-N
InChI=1S/C19H24N2O/c22-19-16-6-2-4-14-3-1-5-15(18(14)16)11-21(19)17-12-20-9-7-13(17)8-10-20/h2,4,6,13,15,17H,1,3,5,7-12H2/t15-,17-/m1/s1

HIDE SMILES / InChI

Molecular Formula C19H24N2O
Molecular Weight 296.4074
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Palonosetron (INN, trade name Aloxi) is a 5-HT3 antagonist used in the prevention and treatment of postoperative and chemotherapy-induced nausea and vomiting (PONV and CINV). Palonosetron is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. Cancer chemotherapy may be associated with a high incidence of nausea and vomiting, particularly when certain agents, such as cisplatin, are used. 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine and that the released serotonin then activates 5-HT3 receptors located on vagal afferents to initiate the vomiting reflex. Postoperative nausea and vomiting is influenced by multiple patients, surgical and anesthesia-related factors and is triggered by the release of 5-HT in a cascade of neuronal events involving both the central nervous system and the gastrointestinal tract. The 5-HT3 receptor has been demonstrated to selectively participate in the emetic response. The most common adverse effects are a headache, which occurs in 4–11% of patients, and constipation in up to 6% of patients. In less than 1% of patients, other gastrointestinal disorders occur, as well as sleeplessness, first- and second-degree atrioventricular block, muscle pain and shortness of breath. Palonosetron is similarly well tolerated as other sections, and slightly less than placebo.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.83 nM [IC50]
0.83 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ALOXI

Approved Use

ALOXI is a serotonin-3 (5-HT3) receptor antagonist indicated in adults for: Moderately emetogenic cancer chemotherapy --prevention of acute and delayed nausea and vomiting associated with initial and repeat courses (1.1) Highly emetogenic cancer chemotherapy -- prevention of acute nausea and vomiting associated with initial and repeat courses (1.1) Prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated (1.3) ALOXI is indicated in pediatric patients aged 1 month to less than 17 years for: Prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy (1.2) 1.1 Chemotherapy-Induced Nausea and Vomiting in Adults ALOXI is indicated for: Moderately emetogenic cancer chemotherapy --prevention of acute and delayed nausea and vomiting associated with initial and repeat courses Highly emetogenic cancer chemotherapy -- prevention of acute nausea and vomiting associated with initial and repeat courses 1.2 Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients Aged 1 Month to Less than 17 Years ALOXI is indicated for prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy. 1.3 Postoperative Nausea and Vomiting in Adults ALOXI is indicated for prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated. As with other antiemetics, routine prophylaxis is not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and vomiting must be avoided during the postoperative period, ALOXI is recommended even where the incidence of postoperative nausea and/or vomiting is low.

Launch Date

1.05909119E12
Secondary
ALOXI

Approved Use

ALOXI is a serotonin-3 (5-HT3) receptor antagonist indicated in adults for: Moderately emetogenic cancer chemotherapy --prevention of acute and delayed nausea and vomiting associated with initial and repeat courses (1.1) Highly emetogenic cancer chemotherapy -- prevention of acute nausea and vomiting associated with initial and repeat courses (1.1) Prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated (1.3) ALOXI is indicated in pediatric patients aged 1 month to less than 17 years for: Prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy (1.2) 1.1 Chemotherapy-Induced Nausea and Vomiting in Adults ALOXI is indicated for: Moderately emetogenic cancer chemotherapy --prevention of acute and delayed nausea and vomiting associated with initial and repeat courses Highly emetogenic cancer chemotherapy -- prevention of acute nausea and vomiting associated with initial and repeat courses 1.2 Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients Aged 1 Month to Less than 17 Years ALOXI is indicated for prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy. 1.3 Postoperative Nausea and Vomiting in Adults ALOXI is indicated for prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated. As with other antiemetics, routine prophylaxis is not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and vomiting must be avoided during the postoperative period, ALOXI is recommended even where the incidence of postoperative nausea and/or vomiting is low.

Launch Date

1.05909119E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5630 ng/L
3 μg/kg bw 1 times / day multiple, intravenous
dose: 3 μg/kg bw
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PALONOSETRON plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
35.8 μg × h/L
3 μg/kg bw 1 times / day multiple, intravenous
dose: 3 μg/kg bw
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PALONOSETRON plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
40 h
unknown, unknown
PALONOSETRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
38%
3 μg/kg bw 1 times / day multiple, intravenous
dose: 3 μg/kg bw
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PALONOSETRON plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
0.75 mg single, intravenous (max)
Recommended
Dose: 0.75 mg
Route: intravenous
Route: single
Dose: 0.75 mg
Co-administed with::
(chemotherapy)
Sources:
unhealthy, adult
n = 667
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 667
Sources:
Disc. AE: Headache...
AEs leading to
discontinuation/dose reduction:
Headache (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Headache 1 patient
Disc. AE
0.75 mg single, intravenous (max)
Recommended
Dose: 0.75 mg
Route: intravenous
Route: single
Dose: 0.75 mg
Co-administed with::
(chemotherapy)
Sources:
unhealthy, adult
n = 667
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 667
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer








Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Palonosetron (Aloxi): a second-generation 5-HT₃ receptor antagonist for chemotherapy-induced nausea and vomiting.
2006 Oct
Patents

Sample Use Guides

Adults 0.25 mg x 1 Infuse over 30 seconds beginning approx. 30 min before the start of chemotherapy. Pediatrics (1 month to less than 17 years) 20 micrograms per kilogram (max 1.5 mg) x 1 Infuse over 15 minutes beginning approx. 30 min before the start of chemotherapy
Route of Administration: Intravenous
NG108-15 cells, known to express both 5-HT3 and NK-1 receptors, were grown in high-glucose Dulbecco’s modified Eagle’s medium supplemented with a mixture of sodium hypoxanthine, aminopterin, and thymidine, 10% heat-inactivated fetal bovine serum, and 2 mM glutamine to 90% confluence. Cells were incubated with palonosetron (10 nM), granisetron (60 nM), and ondansetron (300 nM) for 2 h. Antagonist concentrations were approximately 50-fold Kd in each case to make sure receptors were saturated. Subsequently, antagonists were removed and cells were incubated with growth media without antagonist for an additional hour to allow for dissociation of antagonists still bound to the cell. Next, cell media were replaced with isosmotic HEPES buffer (20 mM, pH 7.4, 130 mM NaCl, 2 mM KCl, 1 mM MgCl2, and 2 mM CaCl2) containing 2 M Fluo-4 acetoxymethyl (AM) ester and pluronic acid (0.04%). Pluronic acid was added as nonionic surfactant to sequester the AM ester molecules into micelles for cell uptake. Cells were incubated for 1 h to allow for cell uptake of the AM ester. Cells were then incubated with SP at various concentrations for 1 h in HEPES buffer without the AM ester and pluronic acid. Subsequently, measurement of calcium-ion release caused by SP alone or SP plus serotonin (107 M final concentration added immediately before measurement) was made by using a fluorometric imaging plate reader.
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:02:53 UTC 2021
Edited
by admin
on Fri Jun 25 22:02:53 UTC 2021
Record UNII
5D06587D6R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PALONOSETRON
INN   VANDF   WHO-DD  
INN  
Official Name English
PALONOSETRON [WHO-DD]
Common Name English
NSC-743769
Code English
PALONOSETRON, (3AS, 3S)-
Common Name English
PALONOSETRON [VANDF]
Common Name English
PALONOSETRON [MI]
Common Name English
PALONOSETRON [INN]
Common Name English
1H-BENZ(DE)ISOQUINOLIN-1-ONE, 2-(3S)-1-AZABICYCLO(2.2.2)OCT-3-YL-2,3,3A,4,5,6-HEXAHYDRO-, (3AS)-
Systematic Name English
(-)-PALONOSETRON
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS PALONOSETRON ACCORD (AUTHORIZED: CANCER, NAUSEA, VOMITING)
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
NDF-RT N0000175818
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
NCI_THESAURUS C267
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
WHO-VATC QA04AA05
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
NDF-RT N0000175817
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
WHO-ATC A04AA05
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
WHO-ATC A04AA55
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
LIVERTOX 733
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
NCI_THESAURUS C94726
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
Code System Code Type Description
IUPHAR
7486
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
PUBCHEM
6337614
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
FDA UNII
5D06587D6R
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
INN
7407
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
EVMPD
SUB09593MIG
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
CAS
135729-61-2
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
DRUG CENTRAL
2046
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
WIKIPEDIA
PALONOSETRON
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
MESH
C083418
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
NCI_THESAURUS
C61874
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
DRUG BANK
DB00377
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
ChEMBL
CHEMBL1189679
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
MERCK INDEX
M8368
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY
RXCUI
70561
Created by admin on Fri Jun 25 22:02:53 UTC 2021 , Edited by admin on Fri Jun 25 22:02:53 UTC 2021
PRIMARY RxNorm
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
TARGET -> AGONIST
BINDING
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> AGONIST
BINDING
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
Related Record Type Details
METABOLITE LESS ACTIVE -> PARENT
The metabolite has less than 1% of the 5-HT3 receptor antagonist activity of palonosetron.
METABOLITE LESS ACTIVE -> PARENT
The metabolite has less than 1% of the 5-HT3 receptor antagonist activity of palonosetron.
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC intravenous administration

Biological Half-life PHARMACOKINETIC Population: Children
PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC