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

Details

Stereochemistry ACHIRAL
Molecular Formula C17H18N4O
Molecular Weight 294.3517
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALOSETRON

SMILES

Cc1c(CN2CCc3c(c4ccccc4n3C)C2=O)[nH]cn1

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 294.3517
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Curator's Comment:: Alosetron does cross the blood-brain barrier.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.29 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

9.5005442E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
9.35 ng/mL
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
14.6 ng/mL
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
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
43.1 ng/mL
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
5 ng/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
24.6 ng × h/mL
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
36.6 ng × h/mL
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
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
66.1 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.45 h
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
1.44 h
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
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
1.65 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
18%
ALOSETRON plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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: Page: S3BA2001
unhealthy, 45
n = 68
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 45
Sex: M+F
Population Size: 68
Sources: Page: S3BA2001
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: Page: S3BA2001
AEs

AEs

AESignificanceDosePopulation
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: Page: S3BA2001
unhealthy, 45
n = 68
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 45
Sex: M+F
Population Size: 68
Sources: Page: S3BA2001
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: Page: S3BA2001
unhealthy, 45
n = 68
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 45
Sex: M+F
Population Size: 68
Sources: Page: S3BA2001
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: Page: S3BA2001
unhealthy, 45
n = 68
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 45
Sex: M+F
Population Size: 68
Sources: Page: S3BA2001
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: Page: S3BA2001
unhealthy, 45
n = 68
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 45
Sex: M+F
Population Size: 68
Sources: Page: S3BA2001
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: Page: S3BA2001
unhealthy, 45
n = 68
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 45
Sex: M+F
Population Size: 68
Sources: Page: S3BA2001
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: Page: S3BA2001
unhealthy, 45
n = 68
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 45
Sex: M+F
Population Size: 68
Sources: Page: S3BA2001
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: Page: S3BA2001
unhealthy, 45
n = 68
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 45
Sex: M+F
Population Size: 68
Sources: Page: S3BA2001
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: Page: S3BA2001
unhealthy, 45
n = 68
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 45
Sex: M+F
Population Size: 68
Sources: Page: S3BA2001
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
yes
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%.
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.
Page: 8.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Adverse drug reaction update.
2002
Contemporary thoughts on the treatment of irritable bowel syndrome.
2002 Aug
The treatment of irritable bowel syndrome.
2002 Aug
Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome.
2002 Aug
From the Food and Drug Administration.
2002 Aug 14
Alosetron (lotronex) revisited.
2002 Aug 5
Patient satisfaction with alosetron for the treatment of women with diarrhea-predominant irritable bowel syndrome.
2002 Dec
Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds.
2002 Jul
FDA approves restricted marketing of Lotronex.
2002 Jul-Aug
Return of alosetron.
2002 May
Systematic review on the management of irritable bowel syndrome in North America.
2002 Nov
Evidence-based position statement on the management of irritable bowel syndrome in North America.
2002 Nov
Excitation of rat colonic afferent fibres by 5-HT(3) receptors.
2002 Nov 1
Gateways to clinical trials.
2002 Oct
FDA OK's two drugs for irritable bowel syndrome. The arsenal of IBS drugs is growing, but diagnosis is tricky.
2002 Oct
Condition-specific deactivation of brain regions by 5-HT3 receptor antagonist Alosetron.
2002 Oct
New developments in the diagnosis and treatment of irritable bowel syndrome.
2002 Oct
Alosetron: a case study in regulatory capture, or a victory for patients' rights?
2002 Sep 14
FDA advisers warn of more deaths if drug is relaunched.
2002 Sep 14
Alosetron for irritable bowel syndrome.
2002 Sep 14
Alosetron in irritable bowel syndrome: strategies for its use in a common gastrointestinal disorder.
2003
Tegaserod and other serotonergic agents: what is the evidence?
2003
Irritable bowel syndrome genophenomics: correlation of serotonin-transporter polymorphisms and alosetron response.
2003
Safety, efficacy and costs of pharmacotherapy for functional gastrointestinal disorders: the case of alosetron and its implications.
2003 Apr
Regulatory role of 5-HT and muscarinic receptor antagonists on the migrating myoelectric complex in rats.
2003 Apr 25
Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron.
2003 Dec
Advances in the management of irritable bowel syndrome.
2003 Dec
Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trials.
2003 Feb
Bad medicine. Why data from drug companies may be hard to swallow.
2003 Feb
[Visceral hypersensitivity: a concept within our reach].
2003 Jan
Alosetron (Lotronex) is back: should I use it to treat my patients with irritable bowel syndrome?
2003 Jan
Lipid-induced colonic hypersensitivity in irritable bowel syndrome: the role of 5-HT3 receptors.
2003 Jan
Alosetron for irritable bowel syndrome. Risks of using alosetron are still unknown.
2003 Jan 4
Alosetron for irritable bowel syndrome. Senior vice president of GlaxoSmithKline responds.
2003 Jan 4
Gateways to clinical trials.
2003 Jan-Feb
Irritable bowel syndrome: an overview of diagnosis and pharmacologic treatment.
2003 Jun
Review: tegaserod or alosetron is effective for the irritable bowel syndrome.
2003 Mar-Apr
Incidence of colonic ischemia, hospitalized complications of constipation, and bowel surgery in relation to use of alosetron hydrochloride.
2003 May
Alosetron and irritable bowel syndrome.
2003 Nov
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
Gateways to clinical trials.
2003 Oct
Evaluation of drug treatment in irritable bowel syndrome.
2003 Oct
Re: Brandt et al.--An evidence-based approach to the management of irritable bowel syndrome in North America.
2003 Sep
Treating irritable bowel syndrome: overview, perspective and future therapies.
2004 Apr
5-HT3-receptor antagonist inhibits visceral pain differently in chemical and mechanical stimuli in rats.
2004 Jan
Study design issues in irritable bowel syndrome.
2004 Jan 1
Safety and tolerability of tegaserod in irritable bowel syndrome management.
2004 Jan-Feb
Occurrence of colon ischemia in relation to irritable bowel syndrome.
2004 Mar
New options for soothing an irritable bowel.
2004 Mar
Therapy for irritable bowel syndrome.
2004 Mar 18
Patents

Patents

Sample Use Guides

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
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 Sat Jun 26 10:09:14 UTC 2021
Edited
by admin
on Sat Jun 26 10:09:14 UTC 2021
Record UNII
13Z9HTH115
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALOSETRON
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
ALOSETRON [MI]
Common Name English
ALOSETRON [VANDF]
Common Name English
A03AE01
Code English
ALOSETRON [INN]
Common Name English
ALOSETRON [WHO-DD]
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
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
WHO-VATC QA03AE01
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
NDF-RT N0000175818
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
LIVERTOX 29
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
WHO-ATC A03AE01
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
NDF-RT N0000175817
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
Code System Code Type Description
MESH
C090840
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
MERCK INDEX
M1574
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY Merck Index
EPA CompTox
122852-42-0
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
IUPHAR
2296
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
NCI_THESAURUS
C73100
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
WIKIPEDIA
ALOSETRON
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
FDA UNII
13Z9HTH115
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
EVMPD
SUB05358MIG
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
DRUG BANK
DB00969
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
DRUG CENTRAL
129
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
ChEMBL
CHEMBL1110
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
RXCUI
85248
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY RxNorm
PUBCHEM
2099
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
CAS
122852-42-0
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
LACTMED
Alosetron
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
INN
6906
Created by admin on Sat Jun 26 10:09:15 UTC 2021 , Edited by admin on Sat Jun 26 10:09:15 UTC 2021
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
Alosetron is metabolized by human microsomal cytochrome P450 (CYP), shown in vitro to involve enzymes 2C9 (30%), 3A4 (18%), and 1A2 (10%).
MAJOR
METABOLIC ENZYME -> SUBSTRATE
Alosetron is metabolized by human microsomal cytochrome P450 (CYP), shown in vitro to involve enzymes 2C9 (30%), 3A4 (18%), and 1A2 (10%).
MAJOR
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
Alosetron is metabolized by human microsomal cytochrome P450 (CYP), shown in vitro to involve enzymes 2C9 (30%), 3A4 (18%), and 1A2 (10%).
MAJOR
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE -> PARENT
in male human urine
URINE
METABOLITE -> PARENT
MINOR
PLASMA
METABOLITE -> PARENT
in female human urine
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC DOSE

ORAL ADMINISTRATION