ALOSETRON

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H18N4O
Molecular Weight	294.351
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C2=CC=CC=C2C3=C1CCN(CC4=C(C)N=CN4)C3=O

InChI

InChIKey=JSWZEAMFRNKZNL-UHFFFAOYSA-N

InChI=1S/C17H18N4O/c1-11-13(19-10-18-11)9-21-8-7-15-16(17(21)22)12-5-3-4-6-14(12)20(15)2/h3-6,10H,7-9H2,1-2H3,(H,18,19)

HIDE SMILES / InChI

Molecular Formula	C17H18N4O
Molecular Weight	294.351
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/2002/21107s5lbl.pdf | https://www.drugs.com/cdi/alosetron.html | https://www.ncbi.nlm.nih.gov/pubmed/10776833

Alosetron, marketed under the brand name Lotronex, is a 5-HT3 antagonist used for the management of severe diarrhea-predominant irritable bowel syndrome (IBS) in women only. Alosetron is a potent and selective 5-HT3 receptor antagonist. 5-HT3 receptors are nonselective cation channels that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit and gastrointestinal secretions, processes that relate to the pathophysiology of irritable bowel syndrome (IBS). 5-HT3 receptor antagonists such as alosetron inhibit activation of non-selective cation channels which results in the modulation of the enteric nervous system. Alosetron is used for the treating women with severe irritable bowel syndrome (IBS) accompanied by severe diarrhea (usually lasting for 6 months or more). It is only prescribed to women who do not respond to other medicines and is not to be used by women whose main IBS problem is constipation.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 3a (5-HT3a) receptor 48 Target ID: CHEMBL1899 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21107s5lbl.pdf	Antagonist 2849		0.29 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Irritable bowel syndrome 61 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21107s5lbl.pdf	Primary		Approved 8583	LOTRONEX Approved Use LOTRONEX is indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have: chronic IBS symptoms (generally lasting 6 months or longer), had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and not responded adequately to conventional therapy. Diarrhea-predominant IBS is severe if it includes diarrhea and one or more of the following: frequent and severe abdominal pain/discomfort, frequent bowel urgency or fecal incontinence, disability or restriction of daily activities due to IBS. Because of infrequent but serious gastrointestinal adverse reactions associated with LOTRONEX, the indication is restricted to those patients for whom the benefit-to-risk balance is most favorable. Clinical studies have not been performed to adequately confirm the benefits of LOTRONEX in men. LOTRONEX is a selective serotonin 5-HT3 antagonist indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have: chronic IBS symptoms (generally lasting 6 months or longer), had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and not responded adequately to conventional therapy. (1) Severe IBS includes diarrhea and 1 or more of the following: frequent and severe abdominal pain/discomfort, frequent bowel urgency or fecal incontinence, disability or restriction of daily activities due to IBS. (1) Launch Date 2000

C_max

Value	Dose	Analyte	Population
43.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
14.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
40.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9.35 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021107s013lbl.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021107s013lbl.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
66.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
36.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
49.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
24.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.65 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1.44 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1.52 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11874386	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	ALOSETRON serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
18% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021107s013lbl.pdf			ALOSETRON plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
8 mg 2 times / day multiple, oral MTD Dose: 8 mg, 2 times / day Route: oral Route: multiple Dose: 8 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf	Disc. AE: Constipation, Gastrointestinal discomfort... AEs leading to discontinuation/dose reduction: Constipation (20%) Gastrointestinal discomfort (3%) Abdominal pain (8%) Nausea (9%) Vomiting (3%) Diarrhea (5%) Headaches (7%) Malaise and fatigue (3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf

AEs

AE	Significance	Dose	Population
Constipation	20% Disc. AE	8 mg 2 times / day multiple, oral MTD Dose: 8 mg, 2 times / day Route: oral Route: multiple Dose: 8 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf
Gastrointestinal discomfort	3% Disc. AE	8 mg 2 times / day multiple, oral MTD Dose: 8 mg, 2 times / day Route: oral Route: multiple Dose: 8 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf
Malaise and fatigue	3% Disc. AE	8 mg 2 times / day multiple, oral MTD Dose: 8 mg, 2 times / day Route: oral Route: multiple Dose: 8 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf
Vomiting	3% Disc. AE	8 mg 2 times / day multiple, oral MTD Dose: 8 mg, 2 times / day Route: oral Route: multiple Dose: 8 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf
Diarrhea	5% Disc. AE	8 mg 2 times / day multiple, oral MTD Dose: 8 mg, 2 times / day Route: oral Route: multiple Dose: 8 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf
Headaches	7% Disc. AE	8 mg 2 times / day multiple, oral MTD Dose: 8 mg, 2 times / day Route: oral Route: multiple Dose: 8 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf
Abdominal pain	8% Disc. AE	8 mg 2 times / day multiple, oral MTD Dose: 8 mg, 2 times / day Route: oral Route: multiple Dose: 8 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf
Nausea	9% Disc. AE	8 mg 2 times / day multiple, oral MTD Dose: 8 mg, 2 times / day Route: oral Route: multiple Dose: 8 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_medr_P15.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057 CYP2E1 1060	CYP1A2 1197 CYP2C8 810 CYP2C19 1119 CYP2E1 729	CYP3A 142 CYP2E1 131 CYP2C19 329

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P4.pdf#page=8 Page: 8.0	inconclusive
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021107s029lbl.pdf#page=5 Page: 5.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P4.pdf#page=8 Page: 8.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P4.pdf#page=8 Page: 8.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P4.pdf#page=8 Page: 8.0	no
CYP2E1 1146	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021107s029lbl.pdf#page=5 Page: 5.0	no
CYP3A 317	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021107s029lbl.pdf#page=5 Page: 5.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P4.pdf#page=8 Page: 8.0	yes
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P4.pdf#page=8 Page: 8.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P3.pdf#page=8 Page: 8.0	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P3.pdf#page=8 Page: 8.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P3.pdf#page=8 Page: 8.0	no
CYP2E1 729	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P3.pdf#page=8 Page: 8.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P3.pdf#page=8 Page: 8.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P3.pdf#page=8 Page: 8.0	yes	unlikely (co-administration study) Comment: Ketoconazole is a known strong inhibitor of CYP3A4. In a pharmacokinetic study, 38 healthy female subjects received ketoconazole 200 mg twice daily for 7 days, with coadministration of alosetron 1 mg on the last day. Ketoconazole increased mean alosetron plasma concentrations (AUC) by 29%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P3.pdf#page=8 Page: 8.0
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P3.pdf#page=8 Page: 8.0	yes	yes (co-administration study) Comment: Fluvoxamine is a known strong inhibitor of CYP1A2 and also inhibits CYP3A4, CYP2C9, and CYP2C19. In a pharmacokinetic study, 40 healthy female subjects received fluvoxamine in escalating doses from 50 to 200 mg/day for 16 days, with coadministration of alosetron 1 mg on the last day. Fluvoxamine increased mean alosetron plasma concentrations (AUC) approximately 6-fold and prolonged the half-life by approximately 3-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21107a_Lotronex_clinphrmr_P3.pdf#page=8 Page: 8.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/12873512/ Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:53783	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:53783
ChemicalBook	CB3107074	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3107074
eMolecules	10222191	https://www.emolecules.com/cgi-bin/more?vid=10222191
eMolecules	14090089	https://www.emolecules.com/cgi-bin/more?vid=14090089

PubMed

Title	Date	PubMed
Pharmacology and clinical experience with alosetron.	2000 Jan	11060667
Effect of alosetron on the pharmacokinetics of fluoxetine.	2001 Apr	11304903
The FDA and The Lancet: an exchange.	2001 Aug 4	11503619
Alosetron improves quality of life in women with diarrhea-predominant irritable bowel syndrome.	2001 Feb	11232690
Management of the irritable bowel syndrome.	2001 Feb	11179242
Lotronex withdrawn from market.	2001 Feb	11175468
Alosetron and the rapid component of delayed rectifying potassium current in cardiac cells.	2001 Feb 23	11263671
Alosetron withdrawn from market.	2001 Jan 1	11194127
Drug therapy options for patients with irritable bowel syndrome.	2001 Jul	11474911
The challenge of irritable bowel syndrome: creating an alliance between patient and physician.	2001 Mar	11263850
[Irritable bowel syndrome: diagnostic criteria and recent advancement of its pharmacological management].	2001 Oct	11680988
The short, sad history of alosetron.	2001 Oct	11560794
Effects of alosetron on spontaneous migrating motor complexes in murine small and large bowel in vitro.	2001 Oct	11557518
Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome.	2001 Sep	11569692
Adverse drug reaction update.	2002	12503258
Contemporary thoughts on the treatment of irritable bowel syndrome.	2002 Aug	12229060
Patient satisfaction with alosetron for the treatment of women with diarrhea-predominant irritable bowel syndrome.	2002 Dec	12492201
Effects of 5-HT(3) antagonism on postprandial gastric volume and symptoms in humans.	2002 Feb	11860405
Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds.	2002 Jul	12184141
Return of alosetron.	2002 May	12904154
Gateways to clinical trials.	2002 Oct	12500432
Tegaserod and other serotonergic agents: what is the evidence?	2003	12776001
Irritable bowel syndrome genophenomics: correlation of serotonin-transporter polymorphisms and alosetron response.	2003	12746730
Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trials.	2003 Feb	12588472
Bad medicine. Why data from drug companies may be hard to swallow.	2003 Feb	12561450
[Visceral hypersensitivity: a concept within our reach].	2003 Jan	12643225
Alosetron (Lotronex) is back: should I use it to treat my patients with irritable bowel syndrome?	2003 Jan	12549728
Lipid-induced colonic hypersensitivity in irritable bowel syndrome: the role of 5-HT3 receptors.	2003 Jan	12534414
Alosetron for irritable bowel syndrome. Risks of using alosetron are still unknown.	2003 Jan 4	12518769
Alosetron for irritable bowel syndrome. Senior vice president of GlaxoSmithKline responds.	2003 Jan 4	12511473
Gateways to clinical trials.	2003 Jan-Feb	12690708

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Irritable Bowel Syndrome -Initial dose: 0.5 mg orally twice a day -Maintenance dose: 0.5 mg orally once or twice a day; can be increased up to 1 mg orally twice a day after 4 weeks of treatment.

Route of Administration: Oral

In Vitro Use Guide

Alosetron blocked the fast 5HT3-mediated depolarisation of guinea-pig myenteric and submucosal neurons in vitro, with half-maximal inhibition at approximately 55 nmol/L.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:14:17 GMT 2025` Edited by `admin` on `Mon Mar 31 18:14:17 GMT 2025`
Record UNII	13Z9HTH115
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

A03AE01

Preferred Name

English

ALOSETRON

Official Name

English

ALOSETRON [MI]

Common Name

English

Alosetron [WHO-DD]

Common Name

English

ALOSETRON [VANDF]

Common Name

English

alosetron [INN]

Common Name

English

1H-PYRIDO(4,3-B)INDOL-1-ONE, 2,3,4,5-TETRAHYDRO-5-METHYL-2-((5-METHYL-1H-IMIDAZOL-4-YL)METHYL)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94726