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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H24N2O.ClH
Molecular Weight 332.868
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PALONOSETRON HYDROCHLORIDE

SMILES

Cl.[H][C@]12CCCC3=C1C(=CC=C3)C(=O)N(C2)[C@@H]4CN5CCC4CC5

InChI

InChIKey=OLDRWYVIKMSFFB-SSPJITILSA-N
InChI=1S/C19H24N2O.ClH/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;1H/t15-,17-;/m1./s1

HIDE SMILES / InChI
Molecular Formula C19H24N2O
Molecular Weight 296.4067
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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.

Originator

Approval Year

2003
176
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 0.83 nM [IC50]
Antagonist
2778
 0.83 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
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
Approved
8429
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
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021372s018s019lbl.pdf
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
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021372s018s019lbl.pdf
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
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021372s018s019lbl.pdf
unknown, unknown
 PALONOSETRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
38%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021372s018s019lbl.pdf
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:
https://pubmed.ncbi.nlm.nih.gov/15139789/
unhealthy, adult
n = 667
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 667
Sources:
https://pubmed.ncbi.nlm.nih.gov/15139789/
Disc. AE: Headache...
AEs leading to
discontinuation/dose reduction:
Headache (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/15139789/
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:
https://pubmed.ncbi.nlm.nih.gov/15139789/
unhealthy, adult
n = 667
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 667
Sources:
https://pubmed.ncbi.nlm.nih.gov/15139789/
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737
inhibitor
1767
substrate
1217

inhibitor
1852

inducer
97
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2A6
707

CYP2B6
810

CYP2E1
882

CYP3A
214
CYP1A2
1054
CYP1A2
701

CYP3A
129
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 no
CYP1A2
1692
 no
CYP2A6
739
 no
CYP2B6
1001
 no
CYP2C9
1819
 no
CYP2D6
1891
 no
CYP2D6
1891
 no
CYP2E1
970
 no
CYP3A
298
 no
CYP3A
298
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2D6
1217
 major
CYP1A2
1054
 minor
CYP3A4
1737
 minor
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:85161
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85161
ChemicalBook
CB32131051
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32131051
ChemicalBook
CB7257940
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7257940
MolPort
MolPort-005-941-486
https://www.molport.com/shop/molecule-link/MolPort-005-941-486
MolPort
MolPort-020-005-893
https://www.molport.com/shop/molecule-link/MolPort-020-005-893
ZINC
ZINC000003795819
http://zinc15.docking.org/substances/ZINC000003795819
PubMed

PubMed

TitleDatePubMed
Patents

Patents

08304544
8
08334388
3
JP2006516976A
30
JP2006516977A
31
JP2007505928A
12
JP2009526755A
447
JP2011236242A
2

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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 Dec 15 15:53:58 UTC 2023
Edited
by admin
on Fri Dec 15 15:53:58 UTC 2023
Record UNII
23310D4I19
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PALONOSETRON HYDROCHLORIDE
EMA EPAR   MART.   MI   ORANGE BOOK   USAN   USP-RS   WHO-DD  
USAN  
Official Name English
PALONOSETRON HYDROCHLORIDE [MI]
Common Name English
PALONOSETRON HCL
Common Name English
PALONOSETRON HYDROCHLORIDE [MART.]
Common Name English
PALONOSETRON HYDROCHLORIDE [USP-RS]
Common Name English
PALONOSETRON HYDROCHLORIDE [JAN]
Common Name English
PALONOSETRON HYDROCHLORIDE [ORANGE BOOK]
Common Name English
AKYNZEO COMPONENT PALONOSETRON HYDROCHLORIDE
Brand Name English
PALONOCETRON HYDROCHLORIDE
JAN  
Common Name English
PALONOSETRON (AS HYDROCHLORIDE)
Common Name English
PALONOSETRON HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
PALONOSETRON HYDROCHLORIDE [USAN]
Common Name English
PALONOSETRON HYDROCHLORIDE [EMA EPAR]
Common Name English
RS-25259-197
Code English
ALOXI
Brand Name English
Palonosetron hydrochloride [WHO-DD]
Common Name English
PALONOSETRON HYDROCHLORIDE COMPONENT OF AKYNZEO
Brand Name English
(3AS)-2,3,3A,4,5,6-HEXAHYDRO-2-((3S)-3-QUINUCLIDINYL)-1H-BENZ(DE)ISOQUINOLIN-1-ONE MONOHYDROCHLORIDE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C94726
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
EMA ASSESSMENT REPORTS PALONOSETRON HOSPERIA (AUTHORIZED: CANCER, NAUSEA, VOMITING)
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
EMA ASSESSMENT REPORTS AKYNZEO (AUTHORIZED: NAUSEA)
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
EMA ASSESSMENT REPORTS ALOXI (AUTHORIZED: VOMITTING)
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
NCI_THESAURUS C267
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
EMA ASSESSMENT REPORTS AKYNZEO (AUTHORIZED: VOMITTING)
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
Code System Code Type Description
CHEBI
85157
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
CAS
135729-62-3
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
MERCK INDEX
m8368
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY Merck Index
FDA UNII
23310D4I19
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
NCI_THESAURUS
C47650
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
USAN
GG-58
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
PUBCHEM
6918303
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
EVMPD
SUB20365
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
ChEMBL
CHEMBL1189679
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
SMS_ID
100000089547
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
RXCUI
397405
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY RxNorm
EPA CompTox
DTXSID8046610
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
DRUG BANK
DBSALT001057
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
DAILYMED
23310D4I19
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
RS_ITEM_NUM
1492200
Created by admin on Fri Dec 15 15:53:58 UTC 2023 , Edited by admin on Fri Dec 15 15:53:58 UTC 2023
PRIMARY
Related Record Type Details
Structure of PALONOSETRON
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of PALONOSETRON N-OXIDE
IMPURITY -> PARENT
Structure of DEHYDRO PALONOSETRON HYDROCHLORIDE
IMPURITY -> PARENT
Structure of PALONOSETRON HYDROCHLORIDE, (3R)-
IMPURITY -> PARENT
Structure of PALONOSETRON HYDROCHLORIDE, (3AR)-
IMPURITY -> PARENT
Structure of DEHYDRO PALONOSETRON N-OXIDE
IMPURITY -> PARENT
Related Record Type Details
Structure of PALONOSETRON
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