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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2022-03-07 02:51:39 UTC
HMDB IDHMDB0014521
Secondary Accession Numbers
  • HMDB14521
Metabolite Identification
Common NamePalonosetron
DescriptionPalonosetron (INN, trade name Aloxi) is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is the most effective of the 5-HT3 antagonists in controlling delayed CINV nausea and vomiting that appear more than 24 hours after the first dose of a course of chemotherapy and is the only drug of its class approved for this use by the U.S. Food and Drug Administration. As of 2008, it is the most recent 5-HT3 antagonist to enter clinical use. [wikipedia]
Structure
Data?1582753189
Synonyms
ValueSource
2-QHBIQOHMDB
Palonosetron, (R-(r*,s*))-isomerHMDB
Palonosetron, (S-(r*,s*))-isomerHMDB
Palonosetron hydrochlorideHMDB
2-(1-Azabicyclo(2.2.2)oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz(de)isoquinolin-1-oneHMDB
AloxiHMDB
Palonosetron, (R-(r*,r*))-isomerHMDB
Chemical FormulaC19H24N2O
Average Molecular Weight296.4067
Monoisotopic Molecular Weight296.1888634
IUPAC Name(5R)-3-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-3-azatricyclo[7.3.1.0⁵,¹³]trideca-1(12),9(13),10-trien-2-one
Traditional Namepalonosetron
CAS Registry Number119904-90-4
SMILES
[H][C@@]12CCCC3=C1C(=CC=C3)C(=O)N(C2)[C@@H]1CN2CCC1CC2
InChI Identifier
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+/m0/s1
InChI KeyCPZBLNMUGSZIPR-DOTOQJQBSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as isoquinolones and derivatives. These are aromatic polycyclic compounds containing a ketone bearing isoquinoline moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsoquinolines and derivatives
Sub ClassIsoquinolones and derivatives
Direct ParentIsoquinolones and derivatives
Alternative Parents
Substituents
  • Isoquinolone
  • Tetrahydroisoquinoline
  • Tetralin
  • Quinuclidine
  • Piperidine
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Amino acid or derivatives
  • Tertiary aliphatic amine
  • Carboxamide group
  • Lactam
  • Tertiary amine
  • Azacycle
  • Carboxylic acid derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Amine
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.46 g/LNot Available
LogP2.7Not Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.46 g/LALOGPS
logP2.72ALOGPS
logP2.55ChemAxon
logS-2.8ALOGPS
pKa (Strongest Basic)7.97ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area23.55 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity88.52 m³·mol⁻¹ChemAxon
Polarizability33.87 ųChemAxon
Number of Rings5ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+166.96231661259
DarkChem[M-H]-165.83831661259
DeepCCS[M-2H]-208.75930932474
DeepCCS[M+Na]+184.11230932474
AllCCS[M+H]+171.532859911
AllCCS[M+H-H2O]+168.432859911
AllCCS[M+NH4]+174.432859911
AllCCS[M+Na]+175.232859911
AllCCS[M-H]-175.732859911
AllCCS[M+Na-2H]-175.332859911
AllCCS[M+HCOO]-174.932859911

Predicted Kovats Retention Indices

Not Available
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Palonosetron GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a59-1930000000-313ee8b58bac090cf92b2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Palonosetron GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Palonosetron GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 10V, Positive-QTOFsplash10-0002-0390000000-1f369979b1f72a5ee2842017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 20V, Positive-QTOFsplash10-03di-0900000000-fb9aedbacdd6c36fc28f2017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 40V, Positive-QTOFsplash10-03di-1900000000-c3e8de8e1e3144a091112017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 10V, Negative-QTOFsplash10-0002-0090000000-863b9de7abaa4a8faed62017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 20V, Negative-QTOFsplash10-0002-0290000000-bc7a738473feda7daae82017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 40V, Negative-QTOFsplash10-0bwi-0920000000-8186e5fa7f2e00ab58222017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 10V, Positive-QTOFsplash10-0002-0090000000-7a52ccd6b135811522742021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 20V, Positive-QTOFsplash10-01ot-0890000000-255810544f96c817dc6b2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 40V, Positive-QTOFsplash10-03dj-0910000000-12f66bfb13295bb786d32021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 10V, Negative-QTOFsplash10-0002-0090000000-6097eef1edfc41faed9b2021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 20V, Negative-QTOFsplash10-0002-0090000000-6097eef1edfc41faed9b2021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Palonosetron 40V, Negative-QTOFsplash10-000i-0930000000-066882119f6fe95ff3f52021-09-23Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00377 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00377 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID130656
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkPalonosetron
METLIN IDNot Available
PubChem Compound148211
PDB IDNot Available
ChEBI ID812387
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Stoltz R, Parisi S, Shah A, Macciocchi A: Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37. [PubMed:15378559 ]
  2. Stoltz R, Cyong JC, Shah A, Parisi S: Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol. 2004 May;44(5):520-31. [PubMed:15102873 ]
  3. Rubenstein EB: Palonosetron: a unique 5-HT3 receptor antagonist indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Clin Adv Hematol Oncol. 2004 May;2(5):284-9. [PubMed:16163194 ]
  4. De Leon A: Palonosetron (Aloxi): a second-generation 5-HT(3) receptor antagonist for chemotherapy-induced nausea and vomiting. Proc (Bayl Univ Med Cent). 2006 Oct;19(4):413-6. [PubMed:17106506 ]
  5. Yang LP, Scott LJ: Palonosetron: in the prevention of nausea and vomiting. Drugs. 2009 Nov 12;69(16):2257-78. doi: 10.2165/11200980-000000000-00000. [PubMed:19852528 ]
  6. Siddiqui MA, Scott LJ: Palonosetron. Drugs. 2004;64(10):1125-32; discussion 1133-4. [PubMed:15139789 ]
  7. Eisenberg P, MacKintosh FR, Ritch P, Cornett PA, Macciocchi A: Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study. Ann Oncol. 2004 Feb;15(2):330-7. [PubMed:14760130 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Stoltz R, Parisi S, Shah A, Macciocchi A: Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37. [PubMed:15378559 ]
  2. Stoltz R, Cyong JC, Shah A, Parisi S: Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol. 2004 May;44(5):520-31. [PubMed:15102873 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Stoltz R, Parisi S, Shah A, Macciocchi A: Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37. [PubMed:15378559 ]
  2. Stoltz R, Cyong JC, Shah A, Parisi S: Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol. 2004 May;44(5):520-31. [PubMed:15102873 ]
  3. Janicki PK: Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Med Sci Monit. 2005 Oct;11(10):RA322-8. Epub 2005 Sep 26. [PubMed:16192915 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Stoltz R, Parisi S, Shah A, Macciocchi A: Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37. [PubMed:15378559 ]
  2. Stoltz R, Cyong JC, Shah A, Parisi S: Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol. 2004 May;44(5):520-31. [PubMed:15102873 ]
General function:
Involved in extracellular ligand-gated ion channel activity
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel
Gene Name:
HTR3A
Uniprot ID:
P46098
Molecular weight:
55279.8
References
  1. Hesketh PJ: New treatment options for chemotherapy-induced nausea and vomiting. Support Care Cancer. 2004 Aug;12(8):550-4. Epub 2004 Jun 30. [PubMed:15232725 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  3. Grunberg SM, Koeller JM: Palonosetron: a unique 5-HT3-receptor antagonist for the prevention of chemotherapy-induced emesis. Expert Opin Pharmacother. 2003 Dec;4(12):2297-303. [PubMed:14640928 ]
  4. Rubenstein EB: Palonosetron: a unique 5-HT3 receptor antagonist indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Clin Adv Hematol Oncol. 2004 May;2(5):284-9. [PubMed:16163194 ]
  5. Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, Macciocchi A, Grunberg S: Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer. 2003 Dec 1;98(11):2473-82. [PubMed:14635083 ]
  6. Stoltz R, Cyong JC, Shah A, Parisi S: Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol. 2004 May;44(5):520-31. [PubMed:15102873 ]
  7. De Leon A: Palonosetron (Aloxi): a second-generation 5-HT(3) receptor antagonist for chemotherapy-induced nausea and vomiting. Proc (Bayl Univ Med Cent). 2006 Oct;19(4):413-6. [PubMed:17106506 ]
  8. Yang LP, Scott LJ: Palonosetron: in the prevention of nausea and vomiting. Drugs. 2009 Nov 12;69(16):2257-78. doi: 10.2165/11200980-000000000-00000. [PubMed:19852528 ]
  9. Navari RM: Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. Future Oncol. 2006 Oct;2(5):591-602. [PubMed:17026451 ]
  10. Gralla R, Lichinitser M, Van Der Vegt S, Sleeboom H, Mezger J, Peschel C, Tonini G, Labianca R, Macciocchi A, Aapro M: Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003 Oct;14(10):1570-7. [PubMed:14504060 ]
  11. Siddiqui MA, Scott LJ: Palonosetron. Drugs. 2004;64(10):1125-32; discussion 1133-4. [PubMed:15139789 ]
  12. Eisenberg P, MacKintosh FR, Ritch P, Cornett PA, Macciocchi A: Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study. Ann Oncol. 2004 Feb;15(2):330-7. [PubMed:14760130 ]
  13. Stoltz R, Parisi S, Shah A, Macciocchi A: Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37. [PubMed:15378559 ]