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

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

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
Implementing evidence based antiemetic guidelines in the oncology setting: results of a 4-month prospective intervention study.	2001 Nov	11762972
The effect of timing of dolasetron administration on its efficacy as a prophylactic antiemetic in the ambulatory setting.	2001 Oct	11574355
Dexamethasone in combination with dolasetron for prophylaxis in the ambulatory setting: effect on outcome after laparoscopic cholecystectomy.	2002 Jun	12170046
Compatibility and stability of 5-HT3 receptor antagonists: a pharmacology review.	2002 Nov-Dec	12432417
[Dolasetron reduces pain on injection of propofol].	2002 Sep	12215937
5-HT3-receptor antagonists and the cytochrome P450 system: clinical implications.	2002 Sep-Oct	12416899
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	14635083
The efficacy and cost-effectiveness of prophylactic 5-hydroxytryptamine3 receptor antagonists: tropisetron, ondansetron and dolasetron.	2003 Feb	12635388
[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
Electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine3 receptor antagonists.	2003 Sep	12921512
Palonosetron.	2004	15139789
Gateways to clinical trials.	2004 Jan-Feb	14988742
Palonosetron: a unique 5-HT3 receptor antagonist indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting.	2004 May	16163194
Single-dose parenteral pharmacological interventions for the prevention of postoperative shivering: a quantitative systematic review of randomized controlled trials.	2004 Sep	15333401
The utility of antiemetics in the prevention and treatment of postoperative nausea and vomiting in patients scheduled for laparoscopic cholecystectomy.	2005	16178752
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
Coronary vasospasm leading to an acute myocardial infarction after the administration of dolasetron.	2005 Feb	15721735
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Docetaxel (Taxotere), cisplatin, UFT, and leucovorin combination chemotherapy in advanced gastric cancer.	2005 Mar 14	15726097
Employment of substandard antiemetic prophylaxis in recent trials of chemotherapy-induced nausea and vomiting.	2005 Nov	16204394
Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting.	2005 Oct	16192915
Prophylaxis of postoperative nausea and vomiting in patients scheduled for breast surgery.	2006	17163275
Pharmacological prophylaxis and management of adult postoperative/postdischarge nausea and vomiting.	2006 Dec	17169748
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
Measuring the maintenance of daily life activities using the functional living index-emesis (FLIE) in patients receiving moderately emetogenic chemotherapy.	2006 Jan	16444851
Prophylaxis of postoperative vomiting in children undergoing tonsillectomy: a systematic review and meta-analysis.	2006 Nov	17005507
Acute gastroenteritis in children: role of anti-emetic medication for gastroenteritis-related vomiting.	2007	17523698
Management of postoperative nausea and vomiting in children.	2007	17291136
Management of radiation-induced nausea and vomiting.	2007 Apr	17379085
Randomized comparison of two anti-emetic strategies in high-risk patients undergoing day-case gynaecological surgery.	2007 Apr	17317757
Tremor in multiple sclerosis.	2007 Feb	17318714
[Dolasetron and shivering. A prospective randomized placebo-controlled pharmaco-economic evaluation].	2007 Jan	17021884
Systemic anticancer therapy in gynecological cancer patients with renal dysfunction.	2007 Jul-Aug	17309673
[Prevention and treatment of postoperative nausea and vomiting in children. An evidence-based approach].	2007 Jun	17521856
A meta-analysis comparing the efficacy of four 5-HT3-receptor antagonists for acute chemotherapy-induced emesis.	2007 Sep	17205281

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 15:43:14 GMT 2023` Edited by `admin` on `Fri Dec 15 15:43:14 GMT 2023`
Record UNII	82WI2L7Q6E
Record Status	`Validated (UNII)`
Record Version

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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