Identification

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Name
Tiotropium
Accession Number
DB01409
Type
Small Molecule
Groups
Approved
Description

Tiotropium is a long-acting, antimuscarinic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD) and asthma.1,2,3,4,5 Tiotropium acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation and bronchodilation.1,2,3,4,5

Tiotropium is more specific for the subset of muscarinic receptors commonly found in the lungs than ipratropium.1

Tiotropium was granted FDA approval on 30 January 2004.2

Structure
Thumb
Synonyms
Not Available
External IDs
BA 679 BR / BA-679 BR
Product Ingredients
IngredientUNIICASInChI Key
Tiotropium bromideXX112XZP0J136310-93-5DQHNAVOVODVIMG-RGECMCKFSA-M
Tiotropium bromide monohydrateL64SXO195N411207-31-3MQLXPRBEAHBZTK-SEINRUQRSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SpirivaCapsule18 ug/1Oral; Respiratory (inhalation)Boehringer Ingelheim2005-10-11Not applicableUs
SpirivaCapsule18 mcgRespiratory (inhalation)Boehringer Ingelheim (Canada) Ltd Ltee2002-11-21Not applicableCanada
SpirivaCapsule18 ug/1Oral; Respiratory (inhalation)Lake Erie Medical &Surgical Supply Dba Quality Care Products Llc2005-10-112014-12-31Us
SpirivaCapsule18 ug/1Oral; Respiratory (inhalation)A-S Medication Solutions2005-10-11Not applicableUs
SpirivaCapsule18 ug/1Oral; Respiratory (inhalation)Physicians Total Care, Inc.2004-07-14Not applicableUs
Spiriva RespimatSolution2.5 mcgRespiratory (inhalation)Boehringer Ingelheim (Canada) Ltd Ltee2014-12-19Not applicableCanada
Spiriva RespimatSpray, metered3.124 ug/1Respiratory (inhalation)Boehringer Ingelheim Pharmaceuticals, Inc.2014-09-30Not applicableUs
Spiriva RespimatSpray, metered1.562 ug/1Respiratory (inhalation)Boehringer Ingelheim Pharmaceuticals, Inc.2015-09-15Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Inspiolto RespimatTiotropium (2.5 mcg) + Olodaterol hydrochloride (2.5 mcg)SolutionRespiratory (inhalation)Boehringer Ingelheim (Canada) Ltd Ltee2015-05-29Not applicableCanada
Stiolto RespimatTiotropium bromide monohydrate (3.124 ug/1) + Olodaterol hydrochloride (2.736 ug/1)Spray, meteredRespiratory (inhalation)Boehringer Ingelheim Pharmaceuticals Inc.2015-05-21Not applicableUs
Categories
UNII
0EB439235F
CAS number
186691-13-4
Weight
Average: 392.512
Monoisotopic: 392.099024577
Chemical Formula
C19H22NO4S2
InChI Key
LERNTVKEWCAPOY-DZZGSBJMSA-N
InChI
InChI=1S/C19H22NO4S2/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/q+1/t11-,12-,13+,16-,17+
IUPAC Name
(1R,2R,4S,5S,7R)-7-{[2-hydroxy-2,2-bis(thiophen-2-yl)acetyl]oxy}-9,9-dimethyl-3-oxa-9-azatricyclo[3.3.1.0^{2,4}]nonan-9-ium
SMILES
[H][C@]12O[C@@]1([H])[C@]1([H])C[C@@]([H])(C[C@@]2([H])[N+]1(C)C)OC(=O)C(O)(C1=CC=CS1)C1=CC=CS1

Pharmacology

Indication

Tiotropium powder for inhalation is indicated for the maintenance of bronchospasm in COPD and to prevent exacerbations of COPD.2 A combination tiotropium and olodaterol metered inhalation spray is indicated for maintenance of COPD.3 A tiotropium inhalation spray is indicated for the maintenance of bronchospasm in COPD, to prevent exacerbations of COPD, and to treat asthma in patients 12 or more years old.4 A tiotropium metered inhalation spray is indicated for the maintenance of bronchospasm in COPD, to prevent exacerbations of COPD, and to treat asthma in patients 6 or more years old.5

Associated Conditions
Pharmacodynamics

Tiotropium is a long acting antimuscarinic that causes bronchodilation.1,2,3,4,5 The effects of tiotropium last over 24 hours and there is a wide therapeutic index as overdoses are uncommon even at doses well above the recommended maximum.2,3,4,5

Mechanism of action

Tiotropium is an antagonist of muscarinic receptors M1 to M5.1,2,3,4,5 Inhibition of the M3 receptor in the smooth muscle of the lungs leads to relaxation of smooth muscle and bronchodilation.1,2,3,4,5

TargetActionsOrganism
AMuscarinic acetylcholine receptor M3
antagonist
Humans
UMuscarinic acetylcholine receptor M1
antagonist
Humans
UMuscarinic acetylcholine receptor M2
antagonist
Humans
UMuscarinic acetylcholine receptor M4Not AvailableHumans
UMuscarinic acetylcholine receptor M5Not AvailableHumans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

33% of an inhaled solution reaches systemic circulation, while oral solutions have a bioavailability of 2-3%.1,3,4,5 A dry powder for inhalation is 19.5% bioavailable.1,2 Tiotropium metered spray for inhalation reaches a maximum concentration in 5-7 minutes.3,4,5

Volume of distribution

The volume of distribution of tiotropium is 32L/kg.1,2,3,4,5

Protein binding

Tiotropium is 72% protein bound in plasma.1,2,3,4,5

Metabolism

Tiotropium is not heavily metabolized in the body.2,3,4,5 74% of an intravenous dose is excreted in the urine as unchanged drug.2,3,4,5 Tiotropium is nonenzymatically cleaved to the inactive metabolites N-methylscopine and dithienylglycolic acid.2,3,4,5 In vitro experiments show cytochrome P-450 dependent oxidation and glutathione conjugation to further metabolites.2,3,4,5

Route of elimination

74% of intravenous tiotropium was excreted unchanged in urine.1,2,3,4,5 14% of a dry powder inhalation dose was excreted unchanged in the urine.1 24 hour urinary excretion after 21 days of 5µg once daily inhalation in patients with COPD is 18.6% and in patients with asthma is 12.8%.2,3,4,5

Half life

The terminal half life of tiotropium is 24 hours in patients with COPD and 44 hours in patients with asthma.4,5

Clearance

The total clearance of tiotropium is 880mL/min in healthy subjects receiving 5µg daily.1,2 The renal clearance of tiotropium was 669mL/min.1 Patients <65 years old demonstrated a clearance of 365mL/min while patients ≥65 demonstrated a clearance of 271mL/min.2 This decreased clearance is not associated with increased AUC or Cmax.3,4,5

Toxicity

Symptoms of overdose include altered mental status, tremors, abdominal pain, and severe constipation.2 However, doses of up to 282µg did not lead to systemic anticholinergic effects in a trial of 6 patients.3,4,5 In case of overdose, stop tiotropium and being symptomatic and supportive therapy.2,3,4,5

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Tiotropium.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Tiotropium.
1,10-PhenanthrolineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of Tachycardia can be increased when Tiotropium is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the central nervous system depressant (CNS depressant) activities of Tiotropium.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Tiotropium.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Tiotropium.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Tiotropium.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Tiotropium.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Tiotropium.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

Synthesis Reference

Rolf Banholzer, "Crystalline tiotropium bromide monohydrate, processes for the preparation thereof, and pharmaceutical compositions." U.S. Patent US20020169321, issued November 14, 2002.

US20020169321
General References
  1. Price D, Sharma A, Cerasoli F: Biochemical properties, pharmacokinetics and pharmacological response of tiotropium in chronic obstructive pulmonary disease patients. Expert Opin Drug Metab Toxicol. 2009 Apr;5(4):417-24. doi: 10.1517/17425250902828337 . [PubMed:19292598]
  2. FDA Drug Approval Package: Tiotropium Bromide Powder for Inhalation [Link]
  3. FDA Approved Drug Products: Tiotropium and Olodaterol Metered Inhalation Spray [Link]
  4. FDA Approved Drug Products: Tiotropium Inhalation Spray [Link]
  5. FDA Approved Drug Products: Tiotropium Metered Inhalation Spray [Link]
External Links
PubChem Compound
5487427
PubChem Substance
46504448
ChemSpider
19618474
ChEBI
90960
ChEMBL
CHEMBL1900528
Therapeutic Targets Database
DAP000344
PharmGKB
PA164769056
HET
0HK
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tiotropium
ATC Codes
R03AL06 — Olodaterol and tiotropium bromideR03BB04 — Tiotropium bromideR03BB54 — Tiotropium bromide, combinations
AHFS Codes
  • 12:08.08 — Antimuscarinics Antispasmodics
PDB Entries
4daj / 4u14 / 4u15 / 5cxv / 5dsg

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceHealthy Volunteers1
0CompletedTreatmentChronic Bronchitis / Chronic Obstructive Pulmonary Disease (COPD)1
1Active Not RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD) / Healthy Volunteer Study1
1Active Not RecruitingTreatmentSpinal Cord Injuries (SCI)1
1CompletedBasic ScienceHealthy Volunteers5
1CompletedScreeningChronic Obstructive Pulmonary Disease (COPD)1
1CompletedTreatmentAsthma (Part 1) / COPD (Part 2)1
1CompletedTreatmentAsthma Bronchial / Chronic Obstructive Pulmonary Disease (COPD)1
1CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)6
1CompletedTreatmentCystic Fibrosis (CF)1
1CompletedTreatmentHealthy Volunteers10
1CompletedTreatmentImpaired Renal Function1
1, 2CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)3
2CompletedOtherChronic Obstructive Pulmonary Disease (COPD)1
2CompletedTreatmentAsthma Bronchial10
2CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)32
2CompletedTreatmentCystic Fibrosis (CF)1
2CompletedTreatmentMild to Moderate Chronic Obstructive Pulmonary Disease (COPD)1
2CompletedTreatmentModerate Chronic Obstructive Pulmonary Disease1
2Enrolling by InvitationTreatmentSpinal Cord Injuries (SCI)1
2RecruitingTreatmentDyspnea / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
2WithdrawnTreatmentChronic Obstructive Pulmonary Disease (COPD)1
2, 3Active Not RecruitingTreatmentAsthma Bronchial1
2, 3CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Lung Diseases, Obstructive1
2, 3RecruitingTreatmentAsthma Bronchial1
3Active Not RecruitingTreatmentAsthma Bronchial1
3CompletedTreatmentAsthma Bronchial14
3CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)93
3CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Chronic Obstructive Pulmonary Disease, COPD, Low Peak Inspiratory Flow Rate / Low Peak Inspiratory Flow Rate (PIFR)1
3CompletedTreatmentCystic Fibrosis (CF)1
3Not Yet RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)1
3RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)1
3TerminatedTreatmentChronic Obstructive Pulmonary Disease (COPD)2
3WithdrawnTreatmentAsthma Bronchial1
3WithdrawnTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4Active Not RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)2
4CompletedNot AvailableChronic Obstructive Pulmonary Disease (COPD)3
4CompletedNot AvailableChronic Obstructive Pulmonary Disease (COPD) / Emphysema1
4CompletedBasic ScienceChronic Obstructive Pulmonary Disease (COPD)1
4CompletedDiagnosticObliterative Bronchiolitis1
4CompletedTreatmentAsthma Bronchial3
4CompletedTreatmentAsthma Bronchial / Chronic Obstructive Pulmonary Disease (COPD)1
4CompletedTreatmentBronchitis / Chronic Obstructive Pulmonary Disease (COPD) / Emphysema1
4CompletedTreatmentChronic Bronchitis / Chronic Obstructive Pulmonary Disease (COPD) / Pulmonary Emphysema1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)50
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Exercise1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Healthy Volunteers1
4Enrolling by InvitationTreatmentBronchiectasis / Chronic Obstructive Pulmonary Disease (COPD)1
4Not Yet RecruitingNot AvailableChronic Obstructive Pulmonary Disease (COPD)1
4Not Yet RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)2
4RecruitingBasic ScienceChronic Obstructive Pulmonary Disease (COPD)1
4RecruitingOtherChronic Obstructive Pulmonary Disease (COPD)1
4RecruitingTreatmentAcute Exacerbation of Chronic Obstructive Pulmonary Disease / Chronic Obstructive Pulmonary Disease (COPD)1
4RecruitingTreatmentAsthmatic Bronchitis / Obstruction Airway / Wheezing / Wheezy Bronchitis1
4RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)4
4TerminatedTreatmentChronic Obstructive Pulmonary Disease (COPD)4
4Unknown StatusDiagnosticChronic Obstructive Pulmonary Disease (COPD) / Emphysema / Small Airway Disease1
4Unknown StatusTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4WithdrawnTreatmentAsthma Bronchial1
4WithdrawnTreatmentChronic Obstructive Pulmonary Disease (COPD)2
Not AvailableActive Not RecruitingNot AvailableAsthma Bronchial1
Not AvailableCompletedNot AvailableAsthma Bronchial2
Not AvailableCompletedNot AvailableAsthma Bronchial / BMI >30 kg/m21
Not AvailableCompletedNot AvailableBronchodilation / Cardiovascular Disease (CVD) / Chronic Obstructive Pulmonary Disease (COPD) / Smoking1
Not AvailableCompletedNot AvailableChronic Obstructive Pulmonary Disease (COPD)17
Not AvailableCompletedSupportive CareChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableCompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)2
Not AvailableNot Yet RecruitingNot AvailableChronic Obstructive Pulmonary Disease (COPD)2
Not AvailableNot Yet RecruitingTreatmentAsthma-chronic obstructive pulmonary disease overlap syndrome1
Not AvailableNot Yet RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableRecruitingNot AvailableAsthma Bronchial1
Not AvailableRecruitingNot AvailableChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableRecruitingPreventionAcute Exacerbation of Chronic Obstructive Pulmonary Disease / Air Pollution1
Not AvailableRecruitingPreventionAirway Remodelling1
Not AvailableTerminatedTreatmentAsthma Bronchial1
Not AvailableUnknown StatusNot AvailableChronic Obstructive Pulmonary Disease (COPD) / Emphysema1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Boehringer Ingelheim Ltd.
  • Diversified Healthcare Services Inc.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
SolutionRespiratory (inhalation)
CapsuleOral; Respiratory (inhalation)18 ug/1
CapsuleRespiratory (inhalation)18 mcg
SolutionRespiratory (inhalation)2.5 mcg
Spray, meteredRespiratory (inhalation)1.562 ug/1
Spray, meteredRespiratory (inhalation)3.124 ug/1
Spray, meteredRespiratory (inhalation)
Prices
Unit descriptionCostUnit
Spiriva HandiHaler 30 18 mcg capsule Box223.07USD box
Spiriva HandiHaler 5 18 mcg capsule Box63.64USD box
Spiriva HandiHaler 6 18 mcg capsule Box41.99USD box
Spiriva 18 mcg cp-handihaler6.31USD inhaler
Spiriva 18 mcg Capsule2.2USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5478578No1995-12-262012-12-26Us
CA2066248No1998-08-042010-09-08Canada
US6908928Yes2005-06-212022-03-24Us
US7070800Yes2006-07-042022-07-22Us
US8022082Yes2011-09-202026-07-19Us
USRE39820Yes2007-09-042018-07-30Us
US7642268Yes2010-01-052022-03-24Us
US7694676Yes2010-04-132027-09-12Us
US6777423Yes2004-08-172022-03-24Us
US7309707Yes2007-12-182022-03-24Us
USRE38912Yes2005-12-062022-04-11Us
US6453795Yes2002-09-242017-06-05Us
US8733341Yes2014-05-272031-04-16Us
US9027967Yes2015-05-122027-10-01Us
US7104470Yes2006-09-122017-04-04Us
US7246615Yes2007-07-242016-12-01Us
US7896264Yes2011-03-012025-11-26Us
US7988001Yes2011-08-022022-02-04Us
US7802568Yes2010-09-282019-08-26Us
US6149054Yes2000-11-212017-06-16Us
US6726124Yes2004-04-272017-04-04Us
US7396341Yes2008-07-082027-04-10Us
US6846413Yes2005-01-252019-02-28Us
US6176442Yes2001-01-232016-12-01Us
US7837235Yes2010-11-232028-09-13Us
US5964416Yes1999-10-122017-04-04Us
US7284474Yes2007-10-232025-02-26Us
US6977042Yes2005-12-202019-02-28Us
US6988496Yes2006-01-242020-08-23Us
US8044046No2011-10-252023-11-10Us
US8034809No2011-10-112025-05-12Us
US7220742No2007-05-222025-05-12Us
US7491719No2009-02-172023-11-10Us
US7056916No2006-06-062023-12-07Us
US7727984No2010-06-012023-11-10Us
US7786111No2010-08-312023-11-10Us
US9010323No2015-04-212030-04-19Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP-1.8ChemAxon
pKa (Strongest Acidic)10.35ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area59.06 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity109.18 m3·mol-1ChemAxon
Polarizability39.52 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9173
Blood Brain Barrier+0.5208
Caco-2 permeable+0.5294
P-glycoprotein substrateSubstrate0.7153
P-glycoprotein inhibitor INon-inhibitor0.7514
P-glycoprotein inhibitor IINon-inhibitor0.9762
Renal organic cation transporterNon-inhibitor0.7256
CYP450 2C9 substrateNon-substrate0.6633
CYP450 2D6 substrateNon-substrate0.7533
CYP450 3A4 substrateSubstrate0.6615
CYP450 1A2 substrateNon-inhibitor0.7787
CYP450 2C9 inhibitorNon-inhibitor0.812
CYP450 2D6 inhibitorNon-inhibitor0.8368
CYP450 2C19 inhibitorNon-inhibitor0.7284
CYP450 3A4 inhibitorNon-inhibitor0.7752
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9289
Ames testNon AMES toxic0.6133
CarcinogenicityNon-carcinogens0.9221
BiodegradationNot ready biodegradable0.9319
Rat acute toxicity2.6249 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9957
hERG inhibition (predictor II)Non-inhibitor0.8947
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as morpholines. These are organic compounds containing a morpholine moiety, which consists of a six-member aliphatic saturated ring with the formula C4H9NO, where the oxygen and nitrogen atoms lie at positions 1 and 4, respectively.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Oxazinanes
Sub Class
Morpholines
Direct Parent
Morpholines
Alternative Parents
Piperidines / N-alkylpyrrolidines / Thiophenes / Tetraalkylammonium salts / Tertiary alcohols / Heteroaromatic compounds / Carboxylic acid esters / Azacyclic compounds / Oxacyclic compounds / Dialkyl ethers
show 10 more
Substituents
Morpholine / Piperidine / N-alkylpyrrolidine / Pyrrolidine / Tetraalkylammonium salt / Quaternary ammonium salt / Heteroaromatic compound / Tertiary alcohol / Thiophene / Carboxylic acid ester
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Hansel TT, Barnes PJ: Tiotropium bromide: a novel once-daily anticholinergic bronchodilator for the treatment of COPD. Drugs Today (Barc). 2002 Sep;38(9):585-600. [PubMed:12582447]
  3. Barnes PJ: Tiotropium bromide. Expert Opin Investig Drugs. 2001 Apr;10(4):733-40. [PubMed:11281822]
  4. Barnes PJ, Belvisi MG, Mak JC, Haddad EB, O'Connor B: Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. Life Sci. 1995;56(11-12):853-9. [PubMed:10188785]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Hansel TT, Barnes PJ: Tiotropium bromide: a novel once-daily anticholinergic bronchodilator for the treatment of COPD. Drugs Today (Barc). 2002 Sep;38(9):585-600. [PubMed:12582447]
  2. Barnes PJ: Tiotropium bromide. Expert Opin Investig Drugs. 2001 Apr;10(4):733-40. [PubMed:11281822]
  3. Barnes PJ, Belvisi MG, Mak JC, Haddad EB, O'Connor B: Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. Life Sci. 1995;56(11-12):853-9. [PubMed:10188785]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Hansel TT, Barnes PJ: Tiotropium bromide: a novel once-daily anticholinergic bronchodilator for the treatment of COPD. Drugs Today (Barc). 2002 Sep;38(9):585-600. [PubMed:12582447]
  2. Barnes PJ, Belvisi MG, Mak JC, Haddad EB, O'Connor B: Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. Life Sci. 1995;56(11-12):853-9. [PubMed:10188785]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Guanyl-nucleotide exchange factor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 Da
References
  1. Glossop PA, Watson CA, Price DA, Bunnage ME, Middleton DS, Wood A, James K, Roberts D, Strang RS, Yeadon M, Perros-Huguet C, Clarke NP, Trevethick MA, Machin I, Stuart EF, Evans SM, Harrison AC, Fairman DA, Agoram B, Burrows JL, Feeder N, Fulton CK, Dillon BR, Entwistle DA, Spence FJ: Inhalation by design: novel tertiary amine muscarinic M(3) receptor antagonists with slow off-rate binding kinetics for inhaled once-daily treatment of chronic obstructive pulmonary disease. J Med Chem. 2011 Oct 13;54(19):6888-904. doi: 10.1021/jm200884j. Epub 2011 Sep 20. [PubMed:21870878]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM5
Uniprot ID
P08912
Uniprot Name
Muscarinic acetylcholine receptor M5
Molecular Weight
60073.205 Da
References
  1. Glossop PA, Watson CA, Price DA, Bunnage ME, Middleton DS, Wood A, James K, Roberts D, Strang RS, Yeadon M, Perros-Huguet C, Clarke NP, Trevethick MA, Machin I, Stuart EF, Evans SM, Harrison AC, Fairman DA, Agoram B, Burrows JL, Feeder N, Fulton CK, Dillon BR, Entwistle DA, Spence FJ: Inhalation by design: novel tertiary amine muscarinic M(3) receptor antagonists with slow off-rate binding kinetics for inhaled once-daily treatment of chronic obstructive pulmonary disease. J Med Chem. 2011 Oct 13;54(19):6888-904. doi: 10.1021/jm200884j. Epub 2011 Sep 20. [PubMed:21870878]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Keam SJ, Keating GM: Tiotropium bromide. A review of its use as maintenance therapy in patients with COPD. Treat Respir Med. 2004;3(4):247-68. [PubMed:15350163]
  2. Mosley JF 2nd, Smith LL, Dutton BN: Tiotropium Bromide/Olodaterol (Stiolto Respimat): Once-Daily Combination Therapy for the Maintenance of COPD. P T. 2016 Feb;41(2):97-102. [PubMed:26908999]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Keam SJ, Keating GM: Tiotropium bromide. A review of its use as maintenance therapy in patients with COPD. Treat Respir Med. 2004;3(4):247-68. [PubMed:15350163]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Nakamura T, Nakanishi T, Haruta T, Shirasaka Y, Keogh JP, Tamai I: Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm. 2010 Feb 1;7(1):187-95. doi: 10.1021/mp900206j. [PubMed:20020740]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Symporter activity
Specific Function
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without...
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Nakamura T, Nakanishi T, Haruta T, Shirasaka Y, Keogh JP, Tamai I: Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm. 2010 Feb 1;7(1):187-95. doi: 10.1021/mp900206j. [PubMed:20020740]

Drug created on July 17, 2007 06:36 / Updated on September 17, 2019 04:06