DOLASETRON MESYLATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H20N2O3.CH4O3S.H2O
Molecular Weight	438.495
Optical Activity	NONE
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=QTFFGPOXNNGTGZ-LIFGOUTFSA-N

InChI=1S/C19H20N2O3.CH4O3S.H2O/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;1-5(2,3)4;/h1-4,9,11-14,20H,5-8,10H2;1H3,(H,2,3,4);1H2/t11-,12-,13+,14+;;

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C19H20N2O3
Molecular Weight	324.3737
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	CH4O3S
Molecular Weight	96.106
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 2778

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 8429	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 1997
Nausea and vomiting associated with moderately emetogenic cancer chemotherapy 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020623s008lbl.pdf	Preventing	Approved 8429	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 1997
Fibromyalgia 89 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21036635	Palliative	Phase III 656	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 1737		substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A 191 UGT 192 FMO 35

Drug as victim

Target	Modality	Activity
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020623s012lbl.pdf#page=2 Page: 2.0	yes
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020623s012lbl.pdf#page=2 Page: 2.0	yes
CYP3A4 1737	substrate 3367 Sources: https://dmd.aspetjournals.org/content/24/5/602.short	yes
FMO 35	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16192915/	yes
UGT 192	substrate 3367 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 1647	inhibitor 1626 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
Efficacy of single-dose intravenous dolasetron versus ondansetron in the prevention of postoperative nausea and vomiting.	2001 Jun	11440292
The effect of anaesthetic technique on postoperative nausea and vomiting after day-case gynaecological laparoscopy.	2002 Apr	12002921
A systematic approach to the management of postoperative nausea and vomiting.	2002 Dec	12476402
Monocomponent chemoembolization in oral and oropharyngeal cancer using an aqueous crystal suspension of cisplatin.	2002 Jan 21	11870505
Dolasetron decreases postoperative nausea and vomiting after breast surgery.	2002 Jul-Aug	12100113
Granisetron vs ondansetron: is it a question of duration of 5-HT3 receptor blockade?	2002 May 20	12085221
Compatibility and stability of 5-HT3 receptor antagonists: a pharmacology review.	2002 Nov-Dec	12432417
Dolasetron for the prevention of postoperative vomiting in children undergoing strabismus surgery.	2003 Jul	12846709
Patient outcomes after therapeutic interchange of dolasetron for granisetron.	2003 May 15	12789874
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
Ondansetron versus dolasetron: a comparison study in the prevention of postoperative nausea and vomiting in patients undergoing gynecological procedures.	2004 Apr	15098526
Timing of administration of dolasetron affects dose necessary to prevent postoperative nausea and vomiting.	2004 Aug	15374558
Carbonyl reduction of naltrexone and dolasetron by oxidoreductases isolated from human liver cytosol.	2004 Dec	15563768
A comparison of infraclavicular nerve block versus general anesthesia for hand and wrist day-case surgeries.	2004 Jul	15220781
Granisetron vs dolasetron for acute chemotherapy-induced nausea and vomiting (CINV) in high and moderately high emetogenic chemotherapy: an open-label pilot study.	2004 Jun	15200746
Single-dose parenteral pharmacological interventions for the prevention of postoperative shivering: a quantitative systematic review of randomized controlled trials.	2004 Sep	15333401
Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same?	2005	15740177
Treatment of postoperative nausea and vomiting with dolasetron versus ondansetron: is there a conflict of interest?	2005 Dec	16301287
Acute emesis: moderately emetogenic chemotherapy.	2005 Feb	15565276
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
The Breast Journal regrettably is retracting a manuscript entitled, " Dolasetron decreases postoperative nausea and vomiting after breast surgery".	2005 Mar-Apr	16363099
Prophylactic intravenous ondansetron and dolasetron in intrathecal morphine-induced pruritus: a randomized, double-blinded, placebo-controlled study.	2005 Nov	16244023
Employment of substandard antiemetic prophylaxis in recent trials of chemotherapy-induced nausea and vomiting.	2005 Nov	16204394
Prevention of postoperative nausea and vomiting with granisetron and dolasetron in relation to CYP2D6 genotype.	2006 Apr	16551910
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	17166262
Lack of effect of aprepitant on hydrodolasetron pharmacokinetics in CYP2D6 extensive and poor metabolizers.	2006 Jul	16809805
Drugs for preventing postoperative nausea and vomiting.	2006 Jul 19	16856030
New antiemetic drugs.	2006 Mar	16608997
Purification and characterization of akr1b10 from human liver: role in carbonyl reduction of xenobiotics.	2006 Mar	16381663
Meta-analysis of the use of rescue antiemetics following PONV prophylactic failure with 5-HT3 antagonist/dexamethasone versus single-agent therapies.	2006 May	16670361
Meta-analysis of the safety of 5-HT3 antagonists with dexamethasone or droperidol for prevention of PONV.	2006 May	16670360
New approaches to chemotherapy-induced nausea and vomiting: from neuropharmacology to clinical investigations.	2006 Sep-Oct	17034670
Management of postoperative nausea and vomiting in children.	2007	17291136

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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:46:47 GMT 2023` Edited by `admin` on `Fri Dec 15 15:46:47 GMT 2023`
Record UNII	U3C8E5BWKR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DOLASETRON MESYLATE

Official Name

English

DOLASETRON MESYLATE [ORANGE BOOK]

Common Name

English

1H-INDOLE-3-CARBOXYLIC ACID, (6R,9AS)-OCTAHYDRO-3-OXO-2,6-METHANO-2H-QUINOLIZIN-8-YL ESTER, REL-, METHANESULFONATE, HYDRATE (1:1:1)

Common Name

English

DOLASETRON MESYLATE [VANDF]

Common Name

English

MDL-73147EF

Code

English

MDL 73,147EF

Code

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.)-, MONOMETHANESULFONATE MONOHYDRATE

Common Name

English

DOLASETRON MESILATE MONOHYDRATE

Common Name

English

ANZEMET

Brand Name

English

DOLASETRON MESYLATE [USP MONOGRAPH]

Common Name

English

DOLASETRON MESYLATE MONOHYDRATE

Common Name

English

DOLASETRON MESYLATE [USAN]

Common Name

English

DOLASETRON MESYLATE [USP-RS]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94726