Identification

Name
Palonosetron
Accession Number
DB00377  (APRD00351)
Type
Small Molecule
Groups
Approved, Investigational
Description

Palonosetron (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.

Structure
Thumb
Synonyms
  • (3aS)-2-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-2,3,3a,4,5,6-hexahydro-1H-benzo[de]isoquinolin-1-one
  • 2-(1-Azabicyclo(2.2.2)oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz(de)isoquinolin-1-one
  • Palonosetron
  • Palonosétron
  • Palonosetrón
  • Palonosetronum
External IDs
2-Qhbiqo / RS 25259 / RS 25259-197
Product Ingredients
IngredientUNIICASInChI Key
Palonosetron hydrochloride23310D4I19135729-62-3OLDRWYVIKMSFFB-SSPJITILSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AloxiInjection, solution250 μgIntravenousHelsinn Birex Pharmaceuticals Ltd.2005-03-22Not applicableEu
AloxiInjection0.25 mg/5mLIntravenousEisai Limited2014-05-28Not applicableUs
AloxiCapsule, gelatin coated0.5 mg/1OralEisai Limited2008-08-222010-05-31Us
AloxiCapsule500 μgOralHelsinn Birex Pharmaceuticals Ltd.2005-03-22Not applicableEu
AloxiSolution0.25 mgIntravenousPurdue Pharma2012-07-19Not applicableCanada
AloxiInjection0.05 mg/1mLIntravenousHelsinn Therapeutics (U.S.), Inc.2018-11-01Not applicableUs
AloxiCapsule500 μgOralHelsinn Birex Pharmaceuticals Ltd.2005-03-22Not applicableEu
AloxiInjection0.075 mg/1.5mLIntravenousEisai Limited2014-05-28Not applicableUs
AloxiCapsule0.5 mgOralPurdue Pharma2012-08-07Not applicableCanada
AloxiInjection0.075 mg/1.5mLIntravenousMGI PHARMA2008-09-23Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PalonosetronInjection, solution0.05 mg/1mLIntravenousNorthStar Rx LLC2018-05-29Not applicableUs
PalonosetronInjection0.25 mg/5mLIntravenousQilu Pharmaceutical Co., Ltd.2018-09-19Not applicableUs
PalonosetronInjection, solution0.05 mg/1mLIntravenousBlue Point Laboratories2018-05-30Not applicableUs
PalonosetronInjection0.25 mg/5mLIntravenousApotex Corp.2018-09-19Not applicableUs
PalonosetronInjection, solution0.25 mg/5mLIntravenousFresenius Kabi USA, LLC2018-09-19Not applicableUs
PalonosetronInjection0.075 mg/1.5mLIntravenousQilu Pharmaceutical Co., Ltd.2018-09-19Not applicableUs
PalonosetronInjection, solution0.05 mg/1mLIntravenousDr.Reddy's Laboratories Limited2018-03-23Not applicableUs
Palonosetron HospiraInjection, solution250 μgIntravenousHospira, Inc.2016-04-08Not applicableEu
Palonosetron HydrochlorideInjection, solution0.05 mg/1mLIntravenousSagent Pharmaceuticals2018-06-15Not applicableUs
Palonosetron HydrochlorideInjection, solution0.075 mg/1.5mLIntravenousHospira, Inc.2018-11-142018-11-14Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AkynzeoPalonosetron (0.5 mg) + Netupitant (300 mg)CapsuleOralPurdue Pharma2017-11-20Not applicableCanada
AkynzeoPalonosetron (0.5 mg/1) + Netupitant (300 mg/1)CapsuleOralHelsinn Therapeutics (U.S.), Inc2014-10-13Not applicableUs
AkynzeoPalonosetron (0.5 mg/1) + Netupitant (300 mg/1)CapsuleOralEisai Limited2014-10-132018-05-31Us
AkynzeoPalonosetron hydrochloride (0.28 mg/1) + Fosnetupitant (260 mg/1)InjectionIntravenousHelsinn Therapeutics (U.S.), Inc2018-04-20Not applicableUs
International/Other Brands
Jiouting (Jiuyuan Gene Engineering) / Onicit (Pfizer) / Palnox (Glenmark) / Paloxi (Kalbe) / Palzen (Dr. Reddy's) / Themiset (Themis Medicare) / Zhiruo (Chia Tai Tianqing)
Categories
UNII
5D06587D6R
CAS number
135729-56-5
Weight
Average: 296.414
Monoisotopic: 296.188863401
Chemical Formula
C19H24N2O
InChI Key
CPZBLNMUGSZIPR-NVXWUHKLSA-N
InChI
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
IUPAC Name
(5S)-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
SMILES
[H][C@]12CCCC3=C1C(=CC=C3)C(=O)N(C2)[C@@H]1CN2CCC1CC2

Pharmacology

Indication

For the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy, as well as prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy. Also used for the prevention of postoperative nausea and vomiting for up to 24 hours post operation.

Associated Conditions
Pharmacodynamics

Palonosetron is an antinauseant and antiemetic agent indicated for the prevention of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and for the prevention of postoperative nausea and vomiting. Palonosetron is a highly specific and selective serotonin 5-HT3 receptor antagonist that is pharmacologically related to other 5-HT3 receptor antagonists, but differs structurally. Palonosetron has a high affinity for 5-HT3 receptors, but has little to no affinity for other receptors. The serontonin 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 suggested that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.

Mechanism of action

Palonosetron is a selective serotonin 5-HT3 receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone. Alternative mechanisms appear to be primarily responsible for delayed nausea and vomiting induced by emetogenic chemotherapy, since similar temporal relationships between between serotonin and emesis beyond the first day after a dose have not been established, and 5-HT3 receptor antagonists generally have not appeared to be effective alone in preventing or ameliorating delayed effects. It has been hypothesized that palonosetron's potency and long plasma half-life may contribute to its observed efficacy in preventing delayed nausea and vomiting caused by moderately emetogenic cancer chemotherapy.

TargetActionsOrganism
A5-hydroxytryptamine receptor 3A
antagonist
Human
Absorption

Low oral bioavailability.

Volume of distribution
  • 8.3 ± 2.5 L/kg
Protein binding

62%

Metabolism

Hepatic (50%), primarily CYP2D6-mediated, although CYP3A4 and CYP1A2 are also involved.

Route of elimination

After a single intravenous dose of 10 mcg/kg [14C]-palonosetron, approximately 80% of the dose was recovered within 144 hours in the urine

Half life

Approximately 40 hours

Clearance
  • 160 +/- 35 mL/h/kg
Toxicity

A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Palonosetron is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Palonosetron is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Palonosetron is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Palonosetron is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Palonosetron is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Palonosetron.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Palonosetron is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Palonosetron is combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Palonosetron.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when Palonosetron is combined with 5-methoxy-N,N-dimethyltryptamine.
Food Interactions
Not Available

References

Synthesis Reference

Pierluigi Rossetto, Peter MacDonald, Ettore Bigatti, Gaia Banfi, Dario Tentorio, "Processes for preparing palonosetron salts." U.S. Patent US20080200681, issued August 21, 2008.

US20080200681
General References
  1. 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]
  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. 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]
  5. Siddiqui MA, Scott LJ: Palonosetron. Drugs. 2004;64(10):1125-32; discussion 1133-4. [PubMed:15139789]
  6. 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]
  7. 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]
External Links
KEGG Drug
D07175
PubChem Compound
6337614
PubChem Substance
46508530
ChemSpider
4892289
BindingDB
50417287
ChEBI
85161
ChEMBL
CHEMBL1189679
Therapeutic Targets Database
DAP000367
PharmGKB
PA10352
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Palonosetron
ATC Codes
A04AA55 — Palonosetron, combinationsA04AA05 — Palonosetron
AHFS Codes
  • 56:22.00 — Antiemetics
FDA label
Download (185 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceNeoplasms Malignant1
1CompletedTreatmentHealthy Adult Male and Female Volunteers1
1, 2CompletedPreventionVomiting1
1, 2CompletedTreatmentMelanoma1
2CompletedPreventionChemotherapy-Induced Nausea and Vomiting (CINV)1
2CompletedPreventionChemotherapy-Induced Nausea and Vomiting (CINV) / Non Hodgkin Lymphoma (NHL)1
2CompletedPreventionMalignancies1
2CompletedPreventionMalignant Gliomas1
2CompletedPreventionNausea / Vomiting1
2CompletedSupportive CareAcute Myelogenous Leukaemia (AML) / Chemotherapy-Induced Nausea and Vomiting (CINV)1
2CompletedSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV)1
2CompletedSupportive CareColorectal Cancers / Nausea and vomiting1
2CompletedSupportive CareMalignant Lymphomas / Myeloma, Plasma-Cell1
2CompletedSupportive CareCancer treatment / Nausea / Vomiting1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentPost-Operative Nausea and Vomiting (PONV)1
2Not Yet RecruitingSupportive CareChemotherapy Induced Nausea Vomiting1
2Not Yet RecruitingSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV) / Lung Cancers1
2RecruitingPreventionChemotherapy Induced Neutropenia / Colo-rectal Cancer1
2RecruitingPreventionChemotherapy-Induced Nausea and Vomiting (CINV)1
2RecruitingSupportive CareHematopoietic Cell Transplantation Recipient / Hematopoietic Stem Cell Transplantation (HSCT) / Nausea / Neoplasms, Malignant / Vomiting1
2TerminatedPreventionNausea / Terminally Ill / Vomiting1
2TerminatedSupportive CareAnal Carcinoma / Carcinoid tumour of the gastrointestinal tract / Carcinoma of the Appendix / Colorectal Cancers / Extrahepatic Bile Duct Cancer / Gallbladder Cancer / Liver Cancer / Malignant Neoplasm of Pancreas / Malignant Neoplasm of Stomach / Nausea and vomiting / Primary Peritoneal Cavity Cancer / Small Intestine Cancer1
2TerminatedSupportive CareBrain Cancer1
2TerminatedSupportive CareNausea and vomiting / Stage III Squamous Cell Carcinoma of the Hypopharynx / Stage III Squamous Cell Carcinoma of the Larynx / Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage III Squamous Cell Carcinoma of the Nasopharynx / Stage III Squamous Cell Carcinoma of the Oropharynx / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Larynx / Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IV Squamous Cell Carcinoma of the Nasopharynx / Stage IV Squamous Cell Carcinoma of the Oropharynx1
2Unknown StatusSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV)1
2Unknown StatusSupportive CareNausea / Vomiting1
2, 3RecruitingPreventionAntiemetics / Antineoplastic Agents / Neoplasms, Breast / Quality of Life1
2, 3RecruitingSupportive CareAdverse Events / Cervical Cancers / Chemotherapy-Induced Nausea and Vomiting (CINV)1
2, 3RecruitingSupportive CareIn Situ Neoplasm / Nausea and Vomiting, Chronic / Neoplasms, Malignant1
3CompletedPreventionChemotherapy-Induced Nausea and Vomiting (CINV)6
3CompletedPreventionNeoplasms1
3CompletedPreventionPost-Operative Nausea and Vomiting (PONV)2
3CompletedSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV) / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedSupportive CareGenital Neoplasms, Female / Nausea / Vomiting1
3CompletedSupportive CareNausea1
3CompletedSupportive CareNausea and vomiting / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
3CompletedTreatmentAdjunct to general anesthesia therapy / Laparoscopic Gynecologic, Abdominal, Other Surgery1
3Not Yet RecruitingSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV)1
3RecruitingPreventionChemotherapy-Induced Nausea and Vomiting (CINV)2
3RecruitingSupportive CareCarcinoma, Breast1
3RecruitingSupportive CareNeoplasms, Malignant1
3RecruitingTreatmentTumors, Solid1
3Unknown StatusPreventionNausea / Vomiting1
4CompletedPreventionAnaesthesia therapy / Palonosetron / Ponv1
4CompletedPreventionNausea / Neoplasms / Vomiting2
4CompletedPreventionPonv1
4CompletedPreventionPost-Operative Nausea and Vomiting (PONV)4
4CompletedSupportive CareMalignancies / Tumors1
4CompletedSupportive CarePonv1
4CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV) / Neoplasms1
4CompletedTreatmentLeukemias / Malignant Lymphomas1
4Not Yet RecruitingPreventionNausea and Vomiting, Postoperative1
Not AvailableCompletedPreventionLaparoscopic Marsupialization of Renal Cyst1
Not AvailableCompletedPreventionMorphine Adverse Reaction1
Not AvailableCompletedPreventionOrthopedic Procedures1
Not AvailableCompletedPreventionAdjunct to general anesthesia therapy / Palonosetron1
Not AvailableCompletedPreventionPost-Operative Nausea and Vomiting (PONV)4
Not AvailableCompletedSupportive CareMale Breast Cancer / Nausea and vomiting / Stage I Breast Carcinoma / Stage II Breast Cancer / Stage IIIA Breast Cancer1
Not AvailableCompletedSupportive CareNausea / Sarcomas / Vomiting1
Not AvailableCompletedSupportive CareNeoplasms, Malignant1
Not AvailableCompletedTreatmentSubstance-Related Disorders1
Not AvailableEnrolling by InvitationPreventionChemotherapy-Induced Nausea and Vomiting (CINV)1
Not AvailableRecruitingNot AvailableChemotherapy-Induced Nausea and Vomiting (CINV)1
Not AvailableRecruitingNot AvailablePalonosetron1
Not AvailableUnknown StatusSupportive CareNon-Hodgkin's Lymphoma (NHL)1

Pharmacoeconomics

Manufacturers
  • Helsinn healthcare sa
Packagers
  • Cardinal Health
  • Catalent Pharma Solutions
  • Eisai Inc.
  • MGI Pharma
  • Oso Biopharmaceuticals Manufacturing LLC
  • Pierre Fabre
  • Sicor Pharmaceuticals
Dosage forms
FormRouteStrength
CapsuleOral
InjectionIntravenous
CapsuleOral0.5 mg
CapsuleOral500 μg
Capsule, gelatin coatedOral0.5 mg/1
InjectionIntravenous0.05 mg/1mL
InjectionIntravenous0.075 mg/1.5mL
InjectionIntravenous0.25 mg/5mL
Injection, solutionIntravenous250 μg
SolutionIntravenous0.25 mg
Injection, solutionIntravenous0.05 mg/1mL
InjectionIntravenous.25 mg/2mL
Injection, solutionIntravenous0.075 mg/1.5mL
Injection, solutionIntravenous0.25 mg/5mL
Prices
Unit descriptionCostUnit
Aloxi 0.075 mg/1.5 ml vial52.8USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9125905Yes2015-09-082024-07-30Us
US8518981Yes2013-08-272024-07-30Us
US7947725Yes2011-05-242024-07-30Us
US8598218Yes2013-12-032024-07-30Us
US7960424Yes2011-06-142024-07-30Us
US9173942Yes2015-11-032024-07-30Us
US7947724Yes2011-05-242024-07-30Us
US8598219Yes2013-12-032024-07-30Us
US8729094Yes2014-05-202024-07-30Us
US9066980Yes2015-06-302024-07-30Us
US9186357No2015-11-172030-11-18Us
US8623826No2014-01-072030-11-18Us
US8951969No2015-02-102030-11-18Us
US6297375No2001-10-022020-02-22Us
US5202333Yes1993-04-132015-10-13Us
US9457020Yes2016-10-042024-07-30Us
US9439854Yes2016-09-132024-07-30Us
US9457021Yes2016-10-042024-07-30Us
US9271975No2016-03-012031-09-09Us
US9943515No2018-04-172030-11-18Us
US9403772No2016-08-022032-05-23Us
US8895586No2014-11-252032-05-23Us
US9908907No2018-03-062032-05-23Us
US9951016No2018-04-242035-09-25Us
US8426450No2013-04-232032-05-23Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.464 mg/mLALOGPS
logP2.72ALOGPS
logP2.55ChemAxon
logS-2.8ALOGPS
pKa (Strongest Basic)7.97ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area23.55 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity88.52 m3·mol-1ChemAxon
Polarizability33.9 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9899
Blood Brain Barrier+0.9953
Caco-2 permeable+0.5986
P-glycoprotein substrateSubstrate0.679
P-glycoprotein inhibitor IInhibitor0.8643
P-glycoprotein inhibitor IINon-inhibitor0.6745
Renal organic cation transporterInhibitor0.5763
CYP450 2C9 substrateNon-substrate0.83
CYP450 2D6 substrateSubstrate0.7618
CYP450 3A4 substrateSubstrate0.6446
CYP450 1A2 substrateInhibitor0.6626
CYP450 2C9 inhibitorNon-inhibitor0.541
CYP450 2D6 inhibitorNon-inhibitor0.7502
CYP450 2C19 inhibitorInhibitor0.9367
CYP450 3A4 inhibitorInhibitor0.6002
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7828
Ames testNon AMES toxic0.8664
CarcinogenicityNon-carcinogens0.9557
BiodegradationNot ready biodegradable0.9762
Rat acute toxicity2.7383 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.883
hERG inhibition (predictor II)Inhibitor0.6891
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0190000000-ae8443b987d38522ce30

Taxonomy

Description
This compound belongs to the class of organic compounds known as isoquinolones and derivatives. These are aromatic polycyclic compounds containing a ketone bearing isoquinoline moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Isoquinolines and derivatives
Sub Class
Isoquinolones and derivatives
Direct Parent
Isoquinolones and derivatives
Alternative Parents
Tetralins / Tetrahydroisoquinolines / Quinuclidines / Piperidines / Tertiary carboxylic acid amides / Trialkylamines / Lactams / Amino acids and derivatives / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Isoquinolone / Tetrahydroisoquinoline / Tetralin / Quinuclidine / Piperidine / Benzenoid / Tertiary carboxylic acid amide / Amino acid or derivatives / Tertiary aliphatic amine / Carboxamide group
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
azabicycloalkane, organic heterotricyclic compound, delta-lactam (CHEBI:85161)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Voltage-gated potassium 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-gate...
Gene Name
HTR3A
Uniprot ID
P46098
Uniprot Name
5-hydroxytryptamine receptor 3A
Molecular Weight
55279.835 Da
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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase 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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase 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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
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. Palonosetron FDA label [File]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 06:38