U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C19H20N2O3
Molecular Weight 324.3744
Optical Activity NONE
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DOLASETRON

SMILES

c1ccc2c(c1)c(c[nH]2)C(=O)O[C@@]3([H])C[C@@]4([H])C[C@@]5([H])C[C@@]([H])(C3)N4CC5=O

InChI

InChIKey=UKTAZPQNNNJVKR-YXSUXZIUSA-N
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-

HIDE SMILES / InChI
Dolasetron is an antinauseant and antiemetic agent, which is approved as a mesylate salt under the brand name anzement for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses; and for the prevention of postoperative nausea and vomiting. Dolasetron is a highly specific and selective serotonin 5-HT3 receptor antagonist. 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. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine, and that the released serotonin then activates 5-HT3 receptors located on vagal efferents to initiate the vomiting reflex. This drug is not shown to have activity at other known serotonin receptors, and has low affinity for dopamine receptors. Dolasetron mesilate is rapidly reduced by carbonyl reductase to form its major pharmacologically active metabolite reduced dolasetron. In addition dolasetron was in the phase III clinical trials for the investigation, that intravenous using of dolasetron mesilate reduces pain intensity in patients with fibromyalgia.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
ANZEMET

Approved Use

ANZEMET Tablets are indicated for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses in adults and children 2 years and older.

Launch Date

8.7393599E11
Preventing
ANZEMET

Approved Use

ANZEMET Tablets are indicated for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses in adults and children 2 years and older.

Launch Date

8.7393599E11
Palliative
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
320 ng/mL
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
HYDRODOLASETRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
556 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDRODOLASETRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.3 h
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
HYDRODOLASETRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
8.1 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDRODOLASETRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
27%
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
HYDRODOLASETRON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
200 mg single, intravenous
Highest studied dose
Dose: 200 mg
Route: intravenous
Route: single
Dose: 200 mg
Sources: Page: p.33
healthy, 19 - 45
n = 24
Health Status: healthy
Age Group: 19 - 45
Sex: M
Population Size: 24
Sources: Page: p.33
Other AEs: Defect conduction intraventricular...
Other AEs:
Defect conduction intraventricular
Sources: Page: p.33
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources: Page: p.33
healthy, 19 - 45
n = 24
Health Status: healthy
Age Group: 19 - 45
Sex: M
Population Size: 24
Sources: Page: p.33
Other AEs: Defect conduction intraventricular...
Other AEs:
Defect conduction intraventricular
Sources: Page: p.33
100 mg single, oral
Recommended
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Nausea and vomiting associated with cancer chemotherapy
Sources: Page: p.5
Other AEs: QT interval prolonged, Torsade de pointes...
Other AEs:
QT interval prolonged
Torsade de pointes
PR interval prolonged
QRS prolonged
Atrioventricular block (grade 3-5)
Cardiac arrest (grade 3-5)
Arrhythmia ventricular (grade 3-5)
Sources: Page: p.5
AEs

AEs

AESignificanceDosePopulation
Defect conduction intraventricular
200 mg single, intravenous
Highest studied dose
Dose: 200 mg
Route: intravenous
Route: single
Dose: 200 mg
Sources: Page: p.33
healthy, 19 - 45
n = 24
Health Status: healthy
Age Group: 19 - 45
Sex: M
Population Size: 24
Sources: Page: p.33
Defect conduction intraventricular
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources: Page: p.33
healthy, 19 - 45
n = 24
Health Status: healthy
Age Group: 19 - 45
Sex: M
Population Size: 24
Sources: Page: p.33
PR interval prolonged
100 mg single, oral
Recommended
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Nausea and vomiting associated with cancer chemotherapy
Sources: Page: p.5
QRS prolonged
100 mg single, oral
Recommended
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Nausea and vomiting associated with cancer chemotherapy
Sources: Page: p.5
QT interval prolonged
100 mg single, oral
Recommended
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Nausea and vomiting associated with cancer chemotherapy
Sources: Page: p.5
Torsade de pointes
100 mg single, oral
Recommended
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Nausea and vomiting associated with cancer chemotherapy
Sources: Page: p.5
Arrhythmia ventricular grade 3-5
100 mg single, oral
Recommended
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Nausea and vomiting associated with cancer chemotherapy
Sources: Page: p.5
Atrioventricular block grade 3-5
100 mg single, oral
Recommended
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Nausea and vomiting associated with cancer chemotherapy
Sources: Page: p.5
Cardiac arrest grade 3-5
100 mg single, oral
Recommended
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Nausea and vomiting associated with cancer chemotherapy
Sources: Page: p.5
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Implementing evidence based antiemetic guidelines in the oncology setting: results of a 4-month prospective intervention study.
2001 Nov
5-HT(3)-receptor antagonists for the treatment of nausea and vomiting: a reappraisal of their side-effect profile.
2002
The effect of anaesthetic technique on postoperative nausea and vomiting after day-case gynaecological laparoscopy.
2002 Apr
Dolasetron, but not metoclopramide prevents nausea and vomiting in patients undergoing laparoscopic cholecystectomy.
2002 Dec
A systematic approach to the management of postoperative nausea and vomiting.
2002 Dec
[Prophylaxis of Postoperative Nausea and Vomiting FollowingGynaecological Laparoscopy].
2002 Jan
Dolasetron for preventing postanesthetic shivering.
2002 Jan
Monocomponent chemoembolization in oral and oropharyngeal cancer using an aqueous crystal suspension of cisplatin.
2002 Jan 21
Dolasetron decreases postoperative nausea and vomiting after breast surgery.
2002 Jul-Aug
Dexamethasone in combination with dolasetron for prophylaxis in the ambulatory setting: effect on outcome after laparoscopic cholecystectomy.
2002 Jun
Granisetron vs ondansetron: is it a question of duration of 5-HT3 receptor blockade?
2002 May 20
Ondansetron and dolasetron provide equivalent postoperative vomiting control after ambulatory tonsillectomy in dexamethasone-pretreated children.
2002 Nov
Binding interactions of antagonists with 5-hydroxytryptamine3A receptor models.
2003
Benefits and risks of newer treatments for chemotherapy-induced and postoperative nausea and vomiting.
2003
A comparison of the costs and efficacy of ondansetron and dolasetron in the prophylaxis of postoperative vomiting in pediatric patients undergoing ambulatory surgery.
2003 Aug
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.
2003 Dec 1
The efficacy and cost-effectiveness of prophylactic 5-hydroxytryptamine3 receptor antagonists: tropisetron, ondansetron and dolasetron.
2003 Feb
Antiemetic prophylaxis for office-based surgery: are the 5-HT3 receptor antagonists beneficial?
2003 Feb
Dolasetron prophylaxis reduces nausea and postanaesthesia recovery time after remifentanil infusion during monitored anaesthesia care for extracorporeal shock wave lithotripsy.
2003 Feb
Dolasetron for the prevention of postoperative vomiting in children undergoing strabismus surgery.
2003 Jul
Patient outcomes after therapeutic interchange of dolasetron for granisetron.
2003 May 15
[Blocking nociceptive afferents by retrobulbar bupivacaine does not decrease nausea and vomiting after propofol-remifentanil anaesthesia].
2003 Nov
Randomized, double-blind trial of dolasetron versus droperidol for prophylaxis of postoperative nausea and vomiting in patients undergoing TRAM flap breast reconstruction surgery.
2003 Nov
Stability of dolasetron in two oral liquid vehicles.
2003 Nov 1
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.
2003 Nov 17
QT prolongation and fatal arrhythmias: a review of clinical implications and effects of drugs.
2003 Nov-Dec
Comparison of oral dolasetron and ondansetron in the prophylaxis of postoperative nausea and vomiting in children.
2003 Oct
Electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine3 receptor antagonists.
2003 Sep
Impact of nausea and vomiting on quality of life in cancer patients during chemotherapy.
2003 Sep 17
Palonosetron.
2004
Intra-arterial induction high-dose chemotherapy with cisplatin for oral and oropharyngeal cancer: long-term results.
2004 Apr 5
Gateways to clinical trials.
2004 Jan-Feb
Is amiodarone a safe antiarrhythmic to use in supraventricular tachyarrhythmias after lung cancer surgery?
2004 Jun 11
Pharmacokinetics of palonosetron in combination with aprepitant in healthy volunteers.
2005 Apr
Dolasetron versus ondansetron for the treatment of postoperative nausea and vomiting.
2005 Feb
Acute emesis: moderately emetogenic chemotherapy.
2005 Feb
5-hydroxytryptamine type-3 receptor antagonists for chemotherapy-induced and radiotherapy-induced nausea and emesis: can we safely reduce the dose of administered agents?
2005 Jul 1
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Prevention and treatment of postoperative nausea and vomiting.
2005 Jun 15
Docetaxel (Taxotere), cisplatin, UFT, and leucovorin combination chemotherapy in advanced gastric cancer.
2005 Mar 14
Prevention of postoperative nausea and vomiting with granisetron and dolasetron in relation to CYP2D6 genotype.
2006 Apr
Paravertebral blocks provide superior same-day recovery over general anesthesia for patients undergoing inguinal hernia repair.
2006 Apr
Systematic review on the recurrence of postoperative nausea and vomiting after a first episode in the recovery room - implications for the treatment of PONV and related clinical trials.
2006 Dec 13
Relative efficacy of ondansetron, granisetron, dolasetron and palonosetron in controlling acute nausea and vomiting associated with platinum-based chemotherapy.
2006 Jun
Anesthesiologists' practice patterns for treatment of postoperative nausea and vomiting in the ambulatory Post Anesthesia Care Unit.
2006 Jun 1
New antiemetic drugs.
2006 Mar
Purification and characterization of akr1b10 from human liver: role in carbonyl reduction of xenobiotics.
2006 Mar
Prophylaxis of postoperative vomiting in children undergoing tonsillectomy: a systematic review and meta-analysis.
2006 Nov
New approaches to chemotherapy-induced nausea and vomiting: from neuropharmacology to clinical investigations.
2006 Sep-Oct
Acute gastroenteritis in children: role of anti-emetic medication for gastroenteritis-related vomiting.
2007
Patents

Sample Use Guides

Prevention of Cancer Chemotherapy-Induced Nausea and Vomiting. Adults: the recommended oral dosage of ANZEMET (dolasetron mesylate) is 100 mg given within one hour before chemotherapy. Pediatric Patients: the recommended oral dosage in pediatric patients 2 to 16 years of age is 1.8 mg/kg given within one hour before chemotherapy, up to a maximum of 100 mg. Prevention of Postoperative Nausea and Vomiting. Adults: the recommended oral dosage of ANZEMET (dolasetron mesylate) is 100 mg within two hours before surgery. Pediatric Patients: the recommended oral dosage in pediatric patients 2 to 16 years of age is 1.2 mg/kg given within two hours before surgery, up to a maximum of 100 mg. Safety and effectiveness in pediatric patients under 2 years of age have not been established. fibromyalgia: dolasetron (n = 29) 12.5mg/d via the intravenous route on 4 days at baseline (M0), 1 month (M1), 2 months (M2) and 3 months (M3) with follow-up to month 12.
Route of Administration: Other
In Vitro Use Guide
Unknown
Name Type Language
DOLASETRON
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
DOLASETRON [INN]
Common Name English
INDOLE-3-CARBOXYLIC ACID, ESTER WITH (8R)-HEXAHYDRO-8-HYDROXY-2,6-METHANO-2H-QUINOLIZIN-3(4H)-ONE
Common Name English
1H-INDOLE-3-CARBOXYLIC ACID, OCTAHYDRO-3-OXO-2,6-METHANO-2H-QUINOLIZIN-8-YL ESTER, (2.ALPHA.,6.ALPHA.,8.ALPHA.,9A.BETA.)-
Common Name English
DOLASETRON [MI]
Common Name English
DOLASETRON [WHO-DD]
Common Name English
DOLASETRON [VANDF]
Common Name English
DOLASETRON [HSDB]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175817
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
LIVERTOX 321
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
WHO-ATC A04AA04
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
NCI_THESAURUS C94726
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
NDF-RT N0000175818
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
WHO-VATC QA04AA04
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
NCI_THESAURUS C267
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
Code System Code Type Description
MERCK INDEX
M4728
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY Merck Index
CAS
139014-62-3
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
NON-SPECIFIC STEREOCHEMISTRY
ChEMBL
CHEMBL2368925
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY
EPA CompTox
115956-12-2
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY
HSDB
7565
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY
DRUG BANK
DB00757
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY
INN
6780
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY
RXCUI
68091
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
3931
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY
CAS
115956-12-2
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY
MESH
C060344
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY
EVMPD
SUB06352MIG
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY
NCI_THESAURUS
C61735
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY
FDA UNII
82WI2L7Q6E
Created by admin on Sat Jun 26 02:23:48 UTC 2021 , Edited by admin on Sat Jun 26 02:23:48 UTC 2021
PRIMARY