DOLASETRON

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H20N2O3
Molecular Weight	324.3737
Optical Activity	NONE
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C[C@H](C[C@H]3C[C@@H](C1)C(=O)CN23)OC(=O)C4=CNC5=C4C=CC=C5

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020623s008lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/21036635

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 3a (5-HT3a) receptor 46 Target ID: CHEMBL1899 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9341357	Antagonist 2737

Conditions

Condition	Modality	Highest Phase	Product
Postoperative nausea and vomiting 29 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020623s008lbl.pdf	Preventing	Approved 8307	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
Nausea and vomiting associated with moderately emetogenic cancer chemotherapy 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020623s008lbl.pdf	Preventing	Approved 8307	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
Fibromyalgia 89 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21036635	Palliative	Phase III 651	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
320 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
27% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf	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

Dose	Population	Adverse events
200 mg single, intravenous Highest studied dose Dose: 200 mg Route: intravenous Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10086835 Page: p.33	healthy, 19 - 45 n = 24 Health Status: healthy Age Group: 19 - 45 Sex: M Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/10086835 Page: p.33	Other AEs: Defect conduction intraventricular... Other AEs: Defect conduction intraventricular Sources: https://pubmed.ncbi.nlm.nih.gov/10086835 Page: p.33
200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10086835 Page: p.33	healthy, 19 - 45 n = 24 Health Status: healthy Age Group: 19 - 45 Sex: M Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/10086835 Page: p.33	Other AEs: Defect conduction intraventricular... Other AEs: Defect conduction intraventricular Sources: https://pubmed.ncbi.nlm.nih.gov/10086835 Page: p.33
100 mg single, oral Recommended Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Nausea and vomiting associated with cancer chemotherapy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5

AEs

AE	Significance	Dose	Population
Defect conduction intraventricular		200 mg single, intravenous Highest studied dose Dose: 200 mg Route: intravenous Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10086835 Page: p.33	healthy, 19 - 45 n = 24 Health Status: healthy Age Group: 19 - 45 Sex: M Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/10086835 Page: p.33
Defect conduction intraventricular		200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10086835 Page: p.33	healthy, 19 - 45 n = 24 Health Status: healthy Age Group: 19 - 45 Sex: M Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/10086835 Page: p.33
PR interval prolonged		100 mg single, oral Recommended Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Nausea and vomiting associated with cancer chemotherapy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5
QRS prolonged		100 mg single, oral Recommended Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Nausea and vomiting associated with cancer chemotherapy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5
QT interval prolonged		100 mg single, oral Recommended Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Nausea and vomiting associated with cancer chemotherapy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5
Torsade de pointes		100 mg single, oral Recommended Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Nausea and vomiting associated with cancer chemotherapy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5
Arrhythmia ventricular	grade 3-5	100 mg single, oral Recommended Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Nausea and vomiting associated with cancer chemotherapy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5
Atrioventricular block	grade 3-5	100 mg single, oral Recommended Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Nausea and vomiting associated with cancer chemotherapy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5
Cardiac arrest	grade 3-5	100 mg single, oral Recommended Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Nausea and vomiting associated with cancer chemotherapy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020623s010lbl.pdf%2C020624s023lbl.pdf Page: p.5

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670		substrate 1168	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A 188 UGT 183 FMO 35

Drug as victim

Target	Modality	Activity
CYP2D6 1168	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020623s012lbl.pdf#page=2 Page: 2.0	yes
CYP3A 188	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020623s012lbl.pdf#page=2 Page: 2.0	yes
CYP3A4 1670	substrate 3264 Sources: https://dmd.aspetjournals.org/content/24/5/602.short	yes
FMO 35	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/16192915/	yes
UGT 183	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020623s012lbl.pdf#page=2 Page: 2.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 Sources: https://pubmed.ncbi.nlm.nih.gov/11046096/

Sourcing

Vendor/Aggregator	ID	URL
AstaTech	C71510
BOC Sciences	115956-12-2
MolPort	MolPort-046-851-633
PI Chemicals	PI-21727
Sigma Aldrich	CDS021594
Vesino Industrial Co Ltd	VA10755
ZINC	ZINC000000897298	http://zinc15.docking.org/substances/ZINC000000897298
eMolecules	195187818
mcule	MCULE-2311889447

PubMed

Title	Date	PubMed
Randomized open-label trial of dolasetron for the control of nausea and vomiting associated with high-dose chemotherapy with hematopoietic stem cell transplantation.	2001	11569889
Placebo-controlled comparison of dolasetron and metoclopramide in preventing postoperative nausea and vomiting in patients undergoing hysterectomy.	2001 Apr	11350463
[Prophylaxis of nausea and vomiting after thyroid surgery: comparison of oral and intravenous dolasetron with intravenous droperidol and placebo].	2001 Jul	11496617
Efficacy of single-dose intravenous dolasetron versus ondansetron in the prevention of postoperative nausea and vomiting.	2001 Jun	11440292
Dolasetron for chemo nausea.	2001 Mar	11288648
The effect of timing of dolasetron administration on its efficacy as a prophylactic antiemetic in the ambulatory setting.	2001 Oct	11574355
Granisetron vs ondansetron: is it a question of duration of 5-HT3 receptor blockade?	2002 May 20	12085221
[Prevention of post-operative nausea and vomiting. Randomised comparison of dolasetron versus dolasetron plus dexamethasone].	2003 Feb	12624696
Patient outcomes after therapeutic interchange of dolasetron for granisetron.	2003 May 15	12789874
[Blocking nociceptive afferents by retrobulbar bupivacaine does not decrease nausea and vomiting after propofol-remifentanil anaesthesia].	2003 Nov	14600858
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	14595183
Stability of dolasetron in two oral liquid vehicles.	2003 Nov 1	14619116
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	14612892
QT prolongation and fatal arrhythmias: a review of clinical implications and effects of drugs.	2003 Nov-Dec	14624285
Comparison of oral dolasetron and ondansetron in the prophylaxis of postoperative nausea and vomiting in children.	2003 Oct	14580054
Timing of administration of dolasetron affects dose necessary to prevent postoperative nausea and vomiting.	2004 Aug	15374558
Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same?	2005	15740177
Pharmacokinetics of palonosetron in combination with aprepitant in healthy volunteers.	2005 Apr	15899109
Dolasetron versus ondansetron for the treatment of postoperative nausea and vomiting.	2005 Feb	15673860
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Prevention and treatment of postoperative nausea and vomiting.	2005 Jun 15	15947124
Prophylaxis of postoperative nausea and vomiting in patients scheduled for breast surgery.	2006	17163275
Drugs for preventing postoperative nausea and vomiting.	2006 Jul 19	16856030
Relative efficacy of ondansetron, granisetron, dolasetron and palonosetron in controlling acute nausea and vomiting associated with platinum-based chemotherapy.	2006 Jun	16984743
Anesthesiologists' practice patterns for treatment of postoperative nausea and vomiting in the ambulatory Post Anesthesia Care Unit.	2006 Jun 1	16740165
New antiemetic drugs.	2006 Mar	16608997
Meta-analysis of the use of rescue antiemetics following PONV prophylactic failure with 5-HT3 antagonist/dexamethasone versus single-agent therapies.	2006 May	16670361
Prophylaxis of postoperative vomiting in children undergoing tonsillectomy: a systematic review and meta-analysis.	2006 Nov	17005507

Patents

Sample Use Guides

In Vivo Use Guide

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

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

Dolasetron [WHO-DD]

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 [VANDF]

Common Name

English

DOLASETRON [HSDB]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175817