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

Details

Stereochemistry ACHIRAL
Molecular Formula C19H22NO4S2.Br
Molecular Weight 472.416
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIOTROPIUM BROMIDE ANHYDROUS

SMILES

[Br-].[H][C@@]12O[C@]1([H])[C@H]3C[C@H](C[C@@H]2[N+]3(C)C)OC(=O)C(O)(C4=CC=CS4)C5=CC=CS5

InChI

InChIKey=DQHNAVOVODVIMG-FOGIBKMMSA-M
InChI=1S/C19H22NO4S2.BrH/c1-20(2)12-9-11(10-13(20)17-16(12)24-17)23-18(21)19(22,14-5-3-7-25-14)15-6-4-8-26-15;/h3-8,11-13,16-17,22H,9-10H2,1-2H3;1H/q+1;/p-1/t11-,12-,13+,16-,17+;

HIDE SMILES / InChI

Molecular Formula C19H21NO4S2
Molecular Weight 391.504
Charge 0
Count
Stereochemistry EPIMERIC
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula BrH
Molecular Weight 80.912
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021395s040lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/19461900

Tiotropium is a long–acting, antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3–receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies prevention of methacholine–induced bronchoconstriction effects were dose–dependent and lasted longer than 24 hours. The bronchodilation following inhalation of tiotropium is predominantly a site–specific effect. Tiotropium is a muscarinic receptor antagonist, often referred to as an antimuscarinic or anticholinergic agent. Although it does not display selectivity for specific muscarinic receptors, on topical application it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect. Tiotropium is used in the management of chronic obstructive pulmonary disease (COPD).Tiotropium bromide capsules for inhalation are co-promoted by Boehringer-Ingelheim and Pfizer under the trade name Spiriva. It is also manufactured and marketed by Cipla under trade name Tiova.

CNS Activity

Curator's Comment: As tiotropium bromide is electrically charged, it is not absorbed by the gastrointestinal tract and does not pass the blood-brain barrier.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.0316 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SPIRIVA

Approved Use

SPIRIVA HANDIHALER (tiotropium bromide inhalation powder) is indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. SPIRIVA HANDIHALER is indicated to reduce exacerbations in COPD patients.

Launch Date

1.07533441E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
10.5 pg/mL
5 μg 1 times / day steady-state, respiratory
dose: 5 μg
route of administration: Respiratory
experiment type: STEADY-STATE
co-administered:
TIOTROPIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
22.1 pg × h/mL
5 μg 1 times / day steady-state, respiratory
dose: 5 μg
route of administration: Respiratory
experiment type: STEADY-STATE
co-administered:
TIOTROPIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
25 h
5 μg single, respiratory
dose: 5 μg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
TIOTROPIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
28%
5 μg single, respiratory
dose: 5 μg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
TIOTROPIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
90 ug single, respiratory
Overdose
Dose: 90 ug
Route: respiratory
Route: single
Dose: 90 ug
Sources:
unhealthy, 74
n = 1
Health Status: unhealthy
Condition: Atrial fibrillation
Age Group: 74
Sex: M
Population Size: 1
Sources:
Disc. AE: Tachycardia...
AEs leading to
discontinuation/dose reduction:
Tachycardia
Sources:
282 ug single, respiratory
Overdose
Dose: 282 ug
Route: respiratory
Route: single
Dose: 282 ug
Sources: Page: p.5
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.5
2.5 ug 1 times / day multiple, respiratory
Recommended
Dose: 2.5 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 2.5 ug, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Bronchospasm associated with chronic obstructive pulmonary disease
Sources: Page: p.1
Disc. AE: Immediate hypersensitivity reaction, Angioedema...
AEs leading to
discontinuation/dose reduction:
Immediate hypersensitivity reaction
Angioedema
Bronchospasm
Anaphylaxis
Bronchospasm paradoxical
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Tachycardia Disc. AE
90 ug single, respiratory
Overdose
Dose: 90 ug
Route: respiratory
Route: single
Dose: 90 ug
Sources:
unhealthy, 74
n = 1
Health Status: unhealthy
Condition: Atrial fibrillation
Age Group: 74
Sex: M
Population Size: 1
Sources:
Anaphylaxis Disc. AE
2.5 ug 1 times / day multiple, respiratory
Recommended
Dose: 2.5 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 2.5 ug, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Bronchospasm associated with chronic obstructive pulmonary disease
Sources: Page: p.1
Angioedema Disc. AE
2.5 ug 1 times / day multiple, respiratory
Recommended
Dose: 2.5 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 2.5 ug, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Bronchospasm associated with chronic obstructive pulmonary disease
Sources: Page: p.1
Bronchospasm paradoxical Disc. AE
2.5 ug 1 times / day multiple, respiratory
Recommended
Dose: 2.5 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 2.5 ug, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Bronchospasm associated with chronic obstructive pulmonary disease
Sources: Page: p.1
Bronchospasm Disc. AE
2.5 ug 1 times / day multiple, respiratory
Recommended
Dose: 2.5 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 2.5 ug, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Bronchospasm associated with chronic obstructive pulmonary disease
Sources: Page: p.1
Immediate hypersensitivity reaction Disc. AE
2.5 ug 1 times / day multiple, respiratory
Recommended
Dose: 2.5 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 2.5 ug, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Bronchospasm associated with chronic obstructive pulmonary disease
Sources: Page: p.1
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Ba 679 BR, a novel long-acting anticholinergic bronchodilator.
1993
Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases.
2013 May
Patents

Sample Use Guides

The recommended dose of SPIRIVA HANDIHALER (Tiotropium) is two inhalations of the powder contents of one SPIRIVA capsule, once-daily, with the HANDIHALER device. Do not take more than one dose in 24 hours. For administration of SPIRIVA HANDIHALER, a SPIRIVA capsule is placed into the center chamber of the HANDIHALER device. The SPIRIVA capsule is pierced by pressing and releasing the green piercing button on the side of the HANDIHALER device. The tiotropium formulation is dispersed into the air stream when the patient inhales through the mouthpiece
Route of Administration: Respiratory
Tiotropium bromide at > 15 pg/mL inhibited IL-8 production from both BEAS-2B cells and LFs (human lung fibroblasts) after LPS stimulation.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:41:25 UTC 2023
Edited
by admin
on Fri Dec 15 15:41:25 UTC 2023
Record UNII
XX112XZP0J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TIOTROPIUM BROMIDE
INN   MI   USAN   WHO-DD  
INN   USAN  
Preferred Name English
TIOTROPIUM BROMIDE ANHYDROUS
Common Name English
6β,7β-Epoxy-3β-hydroxy-8-methyl-1αH,5αH-tropanium bromide, di-2-thienylglycolate
Common Name English
TIOTROPIUM BROMIDE [MI]
Common Name English
TIOTROPIUM BROMIDE [USAN]
Common Name English
1.ALPHA., 2.BETA., 4.BETA, 5.ALPHA, 7.BETA-7-((HYDROXYDI-2-THIENYLACETYL)OXY)-9,9-DIMETHYL-3-OXA-9-AZONIATRICYCLO(3.3.1.0 SUP(2,4))NONANE BROMIDE
Common Name English
BA 679 BR
Code English
BA-679 BR
Code English
BA-679-BR
Code English
BA-679BR
Code English
Tiotropium bromide [WHO-DD]
Common Name English
3-OXA-9-AZONIATRICYCLO(3.3.1.02,4)NONANE, 7-((HYDROXYDI-2-THIENACETYL)OXY)-9,9-DIMETHYL-, BROMIDE, (1.ALPHA.,2.BETA.,4.BETA.,5.ALPHA.,7.BETA.)-
Common Name English
tiotropium bromide [INN]
Common Name English
TIOTROPIUM BROMIDE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
WHO-ATC R03BB04
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
FDA ORPHAN DRUG 241507
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
NCI_THESAURUS C29704
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
WHO-VATC QR03BB04
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
Code System Code Type Description
FDA UNII
XX112XZP0J
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
DRUG BANK
DBSALT000348
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
EPA CompTox
DTXSID2044214
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
USAN
NN-23
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
CHEBI
90959
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
CHEBI
90960
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
WIKIPEDIA
TIOTROPIUM BROMIDE
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
RXCUI
393575
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY RxNorm
NCI_THESAURUS
C84608
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
ChEMBL
CHEMBL1900528
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
SMS_ID
100000077237
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
DAILYMED
XX112XZP0J
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
EVMPD
SUB11095MIG
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
CAS
136310-93-5
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
RS_ITEM_NUM
1667574
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
MERCK INDEX
m10880
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY Merck Index
INN
6965
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
DRUG CENTRAL
2677
Created by admin on Fri Dec 15 15:41:25 UTC 2023 , Edited by admin on Fri Dec 15 15:41:25 UTC 2023
PRIMARY
Related Record Type Details
SOLVATE->ANHYDROUS
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY