dolasetron Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
serotonin receptor antagonists (5-HT3) 3931 115956-12-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • MDL 73,147EF
  • dolasetron methanesulfonate hydrate
  • dolasetron mesylate hydrate
  • anzemet hydrate
  • anzemet
  • dolasetron
  • anemet
  • dolasetron mesylate
  • dolasetron mesilate
Dolasetron mesylate is an antinauseant and antiemetic agent. Dolasetron mesylate and its active metabolite, hydrodolasetron (MDL 74,156), are selective serotonin 5-HT3 receptor antagonists not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors. The serotonin 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.
  • Molecular weight: 324.38
  • Formula: C19H20N2O3
  • CLOGP: 2.34
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 62.40
  • ALOGS: -3.09
  • ROTB: 3

  • Status: OFM

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.20 g O
0.10 g P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 4.11 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 75 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 2 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 180 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.49 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.13 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Sept. 11, 1997 FDA SANOFI AVENTIS US

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 141.01 23.01 147 3320 335401 46347194
Disease progression 51.01 23.01 47 3420 91253 46591342
Drug ineffective 36.52 23.01 4 3463 677834 46004761
Nausea 35.19 23.01 121 3346 687333 45995262
Off label use 33.06 23.01 81 3386 379760 46302835
Flushing 24.51 23.01 27 3440 64587 46618008
Fatigue 24.24 23.01 99 3368 608598 46073997

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 72.72 28.22 94 1592 357189 29593603
Off label use 40.38 28.22 59 1627 249231 29701561

Pharmacologic Action:

SourceCodeDescription
ATC A04AA04 ALIMENTARY TRACT AND METABOLISM
ANTIEMETICS AND ANTINAUSEANTS
ANTIEMETICS AND ANTINAUSEANTS
Serotonin (5HT3) antagonists
FDA MoA N0000175817 Serotonin 3 Receptor Antagonists
FDA EPC N0000175818 Serotonin-3 Receptor Antagonist
MeSH PA D000932 Antiemetics
MeSH PA D002491 Central Nervous System Agents
MeSH PA D005765 Gastrointestinal Agents
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018490 Serotonin Agents
MeSH PA D012702 Serotonin Antagonists

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Post-Operative Nausea and Vomiting indication 1488000
Prevention of Post-Operative Nausea and Vomiting indication
Torsades de pointes contraindication 31722008
Hypokalemia contraindication 43339004
Chronic heart failure contraindication 48447003
Bradycardia contraindication 48867003
Kidney disease contraindication 90708001 DOID:557
Prolonged QT interval contraindication 111975006
Hypomagnesemia contraindication 190855004
Heart block contraindication 233916004
Chemotherapy-induced nausea and vomiting contraindication 236084000
Congenital long QT syndrome contraindication 442917000
Doxorubicin Induced Cardiomyopathy contraindication
Atrioventricular Conduction Defect contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.91 acidic
pKa2 7.74 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
5-hydroxytryptamine receptor 3A Ion channel ANTAGONIST Ki 7.70 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.23 WOMBAT-PK

External reference:

IDSource
D00725 KEGG_DRUG
878143-33-0 SECONDARY_CAS_RN
4021059 VANDF
4024082 VANDF
C0718607 UMLSCUI
CHEBI:4682 CHEBI
CHEMBL2368924 ChEMBL_ID
CHEMBL2368925 ChEMBL_ID
DB00757 DRUGBANK_ID
6918119 PUBCHEM_CID
C060344 MESH_SUPPLEMENTAL_RECORD_UI
6780 INN_ID
82WI2L7Q6E UNII
215357 RXNORM
11370 MMSL
4630 MMSL
d04214 MMSL
006880 NDDF
006881 NDDF
108421009 SNOMEDCT_US
108422002 SNOMEDCT_US
372488002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ANZEMET HUMAN PRESCRIPTION DRUG LABEL 1 30698-220 TABLET, FILM COATED 50 mg ORAL NDA 20 sections