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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2019-07-23 06:00:59 UTC
HMDB IDHMDB0015026
Secondary Accession Numbers
  • HMDB15026
Metabolite Identification
Common NameGranisetron
DescriptionGranisetron is only found in individuals that have used or taken this drug. It is a serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic and antinauseant for cancer chemotherapy patients. [PubChem]Granisetron is a potent, selective antagonist of 5-HT3 receptors. 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.
Structure
Data?1563861659
Synonyms
ValueSource
SancusoChEMBL
KytrilChEMBL
APF530HMDB
Granisetron baseHMDB
1-Methyl-N-(endo-9-methyl-9-azabicyclo(3.3.1)non-3-yl)-1H-indazole-3-carboxamideMeSH
Hydrochloride, granisetronMeSH
Monohydrochloride, granisetronMeSH
Granisetron hydrochlorideMeSH
Granisetron monohydrochlorideMeSH
Chemical FormulaC18H24N4O
Average Molecular Weight312.4094
Monoisotopic Molecular Weight312.19501141
IUPAC Name1-methyl-N-{9-methyl-9-azabicyclo[3.3.1]nonan-3-yl}-1H-indazole-3-carboxamide
Traditional NameGRAN
CAS Registry Number109889-09-0
SMILES
CN1N=C(C(=O)NC2CC3CCCC(C2)N3C)C2=CC=CC=C12
InChI Identifier
InChI=1S/C18H24N4O/c1-21-13-6-5-7-14(21)11-12(10-13)19-18(23)17-15-8-3-4-9-16(15)22(2)20-17/h3-4,8-9,12-14H,5-7,10-11H2,1-2H3,(H,19,23)
InChI KeyMFWNKCLOYSRHCJ-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as indazole-3-carboxamides. These are aromatic compounds containing an indazole ring system that is substituted at the 3-position with a carboxamide group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzopyrazoles
Sub ClassIndazoles
Direct ParentIndazole-3-carboxamides
Alternative Parents
Substituents
  • Indazole-3-carboxamide
  • 2-heteroaryl carboxamide
  • Pyrazole-5-carboxamide
  • Piperidine
  • Benzenoid
  • Azole
  • Heteroaromatic compound
  • Pyrazole
  • Amino acid or derivatives
  • Carboxamide group
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxylic acid derivative
  • Azacycle
  • Amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological location:

Role

Industrial application:

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point219 °C (hydrochloride salt)Not Available
Boiling PointNot AvailableNot Available
Water Solubility0.43 g/LNot Available
LogP2.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.43 g/LALOGPS
logP2.64ALOGPS
logP1.88ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)14.75ChemAxon
pKa (Strongest Basic)9ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area50.16 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity101.83 m³·mol⁻¹ChemAxon
Polarizability35.39 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-06r2-2940000000-146f2d5e07d055b758bfJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0109000000-232e7ada728ba5e5eb79JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03dr-0917000000-f907d6c8c007ae63ac0bJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000l-3900000000-65402ff64bc089f9409dJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0109000000-940597d64f870c91eba1JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03e9-0916000000-a4c50b145efacab49b7cJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udi-1900000000-fd471a7d475cefc66041JSpectraViewer | MoNA
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00889 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00889 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3390
KEGG Compound IDC07023
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkGranisetron
METLIN IDNot Available
PubChem Compound3510
PDB IDNot Available
ChEBI ID154547
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Tan M: Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2003 Sep;4(9):1563-71. [PubMed:12943486 ]
  2. Gan TJ: Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? CNS Drugs. 2005;19(3):225-38. [PubMed:15740177 ]
  3. Feyer P, Seegenschmiedt MH, Steingraeber M: Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies. Support Care Cancer. 2005 Sep;13(9):671-8. Epub 2005 Jul 26. [PubMed:16044252 ]
  4. MEDSAFE [Link]

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. Tan M: Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2003 Sep;4(9):1563-71. [PubMed:12943486 ]
  2. 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 ]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular weight:
58164.815
References
  1. Nakamura H, Ariyoshi N, Okada K, Nakasa H, Nakazawa K, Kitada M: CYP1A1 is a major enzyme responsible for the metabolism of granisetron in human liver microsomes. Curr Drug Metab. 2005 Oct;6(5):469-80. [PubMed:16248838 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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. Hillsley K, Grundy D: Plasticity in the mesenteric afferent response to cisplatin following vagotomy in the rat. J Auton Nerv Syst. 1999 May 28;76(2-3):93-8. [PubMed:10412832 ]
  2. Turvill JL, Connor P, Farthing MJ: The inhibition of cholera toxin-induced 5-HT release by the 5-HT(3) receptor antagonist, granisetron, in the rat. Br J Pharmacol. 2000 Jul;130(5):1031-6. [PubMed:10882387 ]
  3. Cappelli A, Anzini M, Vomero S, Mennuni L, Makovec F, Doucet E, Hamon M, Menziani MC, De Benedetti PG, Giorgi G, Ghelardini C, Collina S: Novel potent 5-HT(3) receptor ligands based on the pyrrolidone structure: synthesis, biological evaluation, and computational rationalization of the ligand-receptor interaction modalities. Bioorg Med Chem. 2002 Mar;10(3):779-801. [PubMed:11814868 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  5. Gan TJ: Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? CNS Drugs. 2005;19(3):225-38. [PubMed:15740177 ]
  6. Tan M: Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2003 Sep;4(9):1563-71. [PubMed:12943486 ]
  7. Ho KY, Gan TJ: Pharmacology, pharmacogenetics, and clinical efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Curr Opin Anaesthesiol. 2006 Dec;19(6):606-11. [PubMed:17093363 ]
  8. Abdelsayed GG: Management of radiation-induced nausea and vomiting. Exp Hematol. 2007 Apr;35(4 Suppl 1):34-6. [PubMed:17379085 ]
  9. Feyer P, Seegenschmiedt MH, Steingraeber M: Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies. Support Care Cancer. 2005 Sep;13(9):671-8. Epub 2005 Jul 26. [PubMed:16044252 ]