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Record Information
Version3.6
Creation Date2012-09-06 15:16:50 UTC
Update Date2016-02-11 01:30:30 UTC
HMDB IDHMDB14895
Secondary Accession NumbersNone
Metabolite Identification
Common NameDolasetron
DescriptionDolasetron 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. Dolasetron is a highly specific and selective serotonin 5-HT3 receptor antagonist. This drug has not shown to have activity at other known serotonin receptors, and has low affinity for dopamine receptors.
Structure
Thumb
SynonymsNot Available
Chemical FormulaC19H20N2O3
Average Molecular Weight324.3737
Monoisotopic Molecular Weight324.147392516
IUPAC Name(3R)-10-oxo-8-azatricyclo[5.3.1.0³,⁸]undecan-5-yl 1H-indole-3-carboxylate
Traditional Namedolasetron
CAS Registry Number115956-12-2
SMILES
[H][C@]12CC(CC3CC(C1)C(=O)CN23)OC(=O)C1=CNC2=CC=CC=C12
InChI Identifier
InChI=1S/C19H20N2O3/c22-18-10-21-12-5-11(18)6-13(21)8-14(7-12)24-19(23)16-9-20-17-4-2-1-3-15(16)17/h1-4,9,11-14,20H,5-8,10H2/t11?,12-,13?,14?/m1/s1
InChI KeyInChIKey=UKTAZPQNNNJVKR-DBBXXEFVSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as indolecarboxylic acids and derivatives. These are compounds containing a carboxylic acid group (or a derivative thereof) linked to an indole.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassIndolecarboxylic acids and derivatives
Direct ParentIndolecarboxylic acids and derivatives
Alternative Parents
Substituents
  • Indolecarboxylic acid derivative
  • Quinolizidine
  • Quinuclidone
  • Indole
  • Quinuclidine
  • Pyrrole-3-carboxylic acid or derivatives
  • Piperidinone
  • Benzenoid
  • Substituted pyrrole
  • Piperidine
  • Heteroaromatic compound
  • Vinylogous amide
  • Pyrrole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ketone
  • Carboxylic acid ester
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antiemetics
  • Serotonin Antagonists
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point278 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.61e-01 g/LNot Available
LogP2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.26 mg/mLALOGPS
logP2.41ALOGPS
logP2.33ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)12.18ChemAxon
pKa (Strongest Basic)6.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area62.4 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity89.34 m3·mol-1ChemAxon
Polarizability33.69 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00757
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00757
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00757
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID54666
KEGG Compound IDC07866
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkDolasetron
NuGOwiki LinkHMDB14895
Metagene LinkHMDB14895
METLIN IDNot Available
PubChem Compound60654
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Balfour JA, Goa KL: Dolasetron. A review of its pharmacology and therapeutic potential in the management of nausea and vomiting induced by chemotherapy, radiotherapy or surgery. Drugs. 1997 Aug;54(2):273-98. [9257083 ]
  2. Gregory RE, Ettinger DS: 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998 Feb;55(2):173-89. [9506240 ]
  3. 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. [15740177 ]

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. Sanwald P, David M, Dow J: Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Comparison with other indole-containing 5-HT3 antagonists. Drug Metab Dispos. 1996 May;24(5):602-9. [8723743 ]
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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
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. Epub 2009 Nov 24. [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. 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. [16192915 ]
  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. Epub 2009 Nov 24. [19934256 ]
  3. Sanwald P, David M, Dow J: Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Comparison with other indole-containing 5-HT3 antagonists. Drug Metab Dispos. 1996 May;24(5):602-9. [8723743 ]
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Conroy T, Cappelaere P, Fabbro M, Fauser AA, Splinter TA, Spielmann M, Schneider M, Chevallier B, Goupil A, Chauvergne J, et al.: Acute antiemetic efficacy and safety of dolasetron mesylate, a 5-HT3 antagonist, in cancer patients treated with cisplatin. European Dolasetron Study Group. Am J Clin Oncol. 1994 Apr;17(2):97-102. [8141114 ]
  3. Reith MK, Sproles GD, Cheng LK: Human metabolism of dolasetron mesylate, a 5-HT3 receptor antagonist. Drug Metab Dispos. 1995 Aug;23(8):806-12. [7493546 ]
  4. 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. [14635083 ]
  5. Monaca-Charley C, Stojkovic T, Duhamel A, De Seze J, Ferriby D, Vermersch P: Double-blind crossover study with dolasetron mesilate, a 5-HT3 receptor antagonist in cerebellar syndrome secondary to multiple sclerosis. J Neurol. 2003 Oct;250(10):1190-4. [14586600 ]
  6. Boeijinga PH, Galvan M, Baron BM, Dudley MW, Siegel BW, Slone AL: Characterization of the novel 5-HT3 antagonists MDL 73147EF (dolasetron mesilate) and MDL 74156 in NG108-15 neuroblastoma x glioma cells. Eur J Pharmacol. 1992 Aug 14;219(1):9-13. [1397053 ]
  7. Balfour JA, Goa KL: Dolasetron. A review of its pharmacology and therapeutic potential in the management of nausea and vomiting induced by chemotherapy, radiotherapy or surgery. Drugs. 1997 Aug;54(2):273-98. [9257083 ]
  8. Hui YF, Ignoffo RJ: Dolasetron. A new 5-hydroxytryptamine3 receptor antagonist. Cancer Pract. 1997 Sep-Oct;5(5):324-8. [9341357 ]
  9. Gregory RE, Ettinger DS: 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998 Feb;55(2):173-89. [9506240 ]
  10. 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. [15740177 ]