Identification

Name
Tiotropium
Accession Number
DB01409
Type
Small Molecule
Groups
Approved
Description

Tiotropium is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD). Tiotropium is a muscarinic receptor antagonist, on topical application it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect.

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)Lake Erie Medical &Surgical Supply Dba Quality Care Products Llc2005-10-112014-12-31Us
SpirivaCapsule18 mcgRespiratory (inhalation)Boehringer Ingelheim (Canada) Ltd Ltee2002-11-21Not applicableCanada
SpirivaCapsule18 ug/1Oral; Respiratory (inhalation)Physicians Total Care, Inc.2004-07-14Not applicableUs
SpirivaCapsule18 ug/1Oral; Respiratory (inhalation)Boehringer Ingelheim2005-10-11Not applicableUs
Spiriva RespimatSpray, metered1.562 ug/1Respiratory (inhalation)Boehringer Ingelheim2015-09-15Not applicableUs
Spiriva RespimatSolution2.5 mcgRespiratory (inhalation)Boehringer Ingelheim (Canada) Ltd Ltee2014-12-19Not applicableCanada
Spiriva RespimatSpray, metered3.124 ug/1Respiratory (inhalation)Boehringer Ingelheim2014-09-30Not applicableUs
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 Ingelheim2015-05-21Not 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[3.3.1.0²,⁴]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

Used in the management of chronic obstructive pulmonary disease (COPD).

Associated Conditions
Pharmacodynamics

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.

Mechanism of action

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.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M3
antagonist
Human
UMuscarinic acetylcholine receptor M1
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
UMuscarinic acetylcholine receptor M4Not AvailableHuman
UMuscarinic acetylcholine receptor M5Not AvailableHuman
Absorption

Bioavailability is 19.5% following administration by inhalation. Oral solutions of tiotropium have an absolute bioavailability of 2-3%.

Volume of distribution
  • 32 L/kg
Protein binding

72% bound to plasma proteins.

Metabolism

The extent of biotransformation appears to be small. This is evident from a urinary excretion of 74% of unchanged substance after an intravenous dose to young healthy volunteers. Tiotropium, an ester, is nonenzymatically cleaved to the alcohol N–methylscopine and dithienylglycolic acid, neither of which bind to muscarinic receptors. In vitro experiments with human liver microsomes and human hepatocytes suggest that a fraction of the administered dose (74% of an intravenous dose is excreted unchanged in the urine, leaving 25% for metabolism) is metabolized by cytochrome P450–dependent oxidation and subsequent glutathione conjugation to a variety of Phase II metabolites. Via inhibition studies, it is evident that CYP450 2D6 and 3A4 are involved in the metabolic pathway that is responsible for the elimination of a small part of the administered dose.

Route of elimination

Intravenously administered tiotropium was mainly excreted unchanged in urine (74%). After dry powder inhalation, urinary excretion was 14% of the dose, the remainder being mainly non-absorbed drug in the gut which was eliminated via the feces.

Half life

5-6 days

Clearance
  • 880 mL/min [young healthy volunteers receiving IV administration]
  • Renal cl=326 mL/min [COPD patients (<58 years)]
  • Renal cl=163 mL/min [COPD patients (>70 years)]
Toxicity

No mortality was observed at inhalation tiotropium doses up to 32.4 mg/kg in mice, 267.7 mg/kg in rats, and 0.6 mg/kg in dogs. These doses correspond to 7,300, 120,000, and 850 times the recommended human daily dose on a mg/m2 basis, respectively.

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

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with 1,10-Phenanthroline.
AbirateroneThe serum concentration of Tiotropium can be increased when it is combined with Abiraterone.
AcetaminophenAcetaminophen may decrease the excretion rate of Tiotropium which could result in a higher serum level.
Acetyl sulfisoxazoleThe metabolism of Tiotropium can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Tiotropium which could result in a higher serum level.
AclidiniumTiotropium may increase the anticholinergic activities of Aclidinium.
AgmatineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Agmatine.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Tiotropium.
AlcuroniumAlcuronium may increase the anticholinergic activities of Tiotropium.
AlfentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Alfentanil.
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
Not Available
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 bromideR03BB54 — Tiotropium bromide, combinationsR03BB04 — Tiotropium bromide
AHFS Codes
  • 12:08.08 — Antimuscarinics Antispasmodics
PDB Entries
4daj / 4u14 / 4u15 / 5cxv / 5dsg
FDA label
Download (401 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceHealthy Volunteers1
0CompletedTreatmentChronic Bronchitis / Chronic Obstructive Pulmonary Disease (COPD)1
1Active Not RecruitingTreatmentSpinal Cord Injuries (SCI)1
1CompletedBasic ScienceHealthy Volunteers5
1CompletedScreeningPulmonary Disease, Chronic Obstructive1
1CompletedTreatmentAsthma (Part 1) / COPD (Part 2)1
1CompletedTreatmentAsthma Bronchial / Chronic Obstructive Pulmonary Disease (COPD)1
1CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)2
1CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Disease, Chronic Obstructive1
1CompletedTreatmentCystic Fibrosis (CF)1
1CompletedTreatmentHealthy Volunteers7
1CompletedTreatmentImpaired Renal Function1
1CompletedTreatmentPulmonary Disease, Chronic Obstructive3
1, 2CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)3
2CompletedTreatmentAsthma Bronchial6
2CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)7
2CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Disease, Chronic Obstructive1
2CompletedTreatmentCystic Fibrosis (CF)1
2CompletedTreatmentPulmonary Disease, Chronic Obstructive15
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, 3CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Lung Diseases, Obstructive / Pulmonary Disease, Chronic Obstructive1
2, 3RecruitingTreatmentAsthma Bronchial2
3CompletedTreatmentAsthma Bronchial8
3CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)24
3CompletedTreatmentChronic Obstructive Pulmonary Disease, COPD, Low Peak Inspiratory Flow Rate1
3CompletedTreatmentCystic Fibrosis (CF)1
3CompletedTreatmentPulmonary Disease, Chronic Obstructive53
3Not Yet RecruitingTreatmentAsthma Bronchial1
3TerminatedTreatmentPulmonary Disease, Chronic Obstructive2
3WithdrawnTreatmentPulmonary Disease, Chronic Obstructive1
4Active Not RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4Active Not RecruitingTreatmentPulmonary Disease, Chronic Obstructive1
4CompletedNot AvailableChronic Obstructive Pulmonary Disease (COPD) / Emphysema1
4CompletedNot AvailablePulmonary Disease, Chronic Obstructive1
4CompletedBasic ScienceChronic Obstructive Pulmonary Disease (COPD)1
4CompletedDiagnosticObliterative Bronchiolitis1
4CompletedTreatmentAsthma Bronchial2
4CompletedTreatmentBronchitis / Chronic Obstructive Pulmonary Disease (COPD) / Emphysema1
4CompletedTreatmentChronic Bronchitis / Pulmonary Disease, Chronic Obstructive / Pulmonary Emphysema1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)20
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Healthy Volunteers1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Disease, Chronic Obstructive1
4CompletedTreatmentExercise / Pulmonary Disease, Chronic Obstructive1
4CompletedTreatmentPulmonary Disease, Chronic Obstructive18
4Not Yet RecruitingOtherPulmonary Disease, Chronic Obstructive1
4RecruitingBasic ScienceChronic Obstructive Pulmonary Disease (COPD)1
4RecruitingTreatmentAsthmatic Bronchitis / Obstruction Airway / Wheezing / Wheezy Bronchitis1
4RecruitingTreatmentBronchiectasis / Chronic Obstructive Pulmonary Disease (COPD)1
4RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)4
4RecruitingTreatmentPulmonary Disease, Chronic Obstructive5
4TerminatedTreatmentChronic Obstructive Pulmonary Disease (COPD)2
4TerminatedTreatmentPulmonary Disease, Chronic Obstructive2
4Unknown StatusDiagnosticChronic Obstructive Pulmonary Disease (COPD) / Emphysema / Small Airway Disease1
4Unknown StatusTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4WithdrawnTreatmentAsthma Bronchial1
4WithdrawnTreatmentChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableActive Not RecruitingNot AvailableAsthma Bronchial1
Not AvailableCompletedNot AvailableAsthma Bronchial1
Not AvailableCompletedNot AvailableAsthma Bronchial / BMI >30 kg/m21
Not AvailableCompletedNot AvailableBronchodilation / Cardiovascular Disease (CVD) / Chronic Obstructive Pulmonary Disease (COPD) / Smoking1
Not AvailableCompletedNot AvailablePulmonary Disease, Chronic Obstructive14
Not AvailableCompletedSupportive CareChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableCompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableNot Yet RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableRecruitingNot AvailablePulmonary Disease, Chronic Obstructive1
Not AvailableRecruitingPreventionAcute Exacerbation of Chronic Obstructive Pulmonary Disease / Air Pollution1
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)
US5478578No1992-12-262012-12-26Us
CA2066248No1998-08-042010-09-08Canada
US6908928Yes2002-03-242022-03-24Us
US7070800Yes2002-07-222022-07-22Us
US8022082Yes2006-07-192026-07-19Us
USRE39820Yes1998-07-302018-07-30Us
US7642268Yes2002-03-242022-03-24Us
US7694676Yes2007-09-122027-09-12Us
US6777423Yes2002-03-242022-03-24Us
US7309707Yes2002-03-242022-03-24Us
USRE38912Yes2002-04-112022-04-11Us
US6453795Yes1997-06-052017-06-05Us
US8733341Yes2011-04-162031-04-16Us
US9027967Yes2007-10-012027-10-01Us
US7104470Yes1997-04-042017-04-04Us
US7246615Yes1996-12-012016-12-01Us
US7896264Yes2005-11-262025-11-26Us
US7988001Yes2002-02-042022-02-04Us
US7802568Yes1999-08-262019-08-26Us
US6149054Yes1997-06-162017-06-16Us
US6726124Yes1997-04-042017-04-04Us
US7396341Yes2007-04-102027-04-10Us
US6846413Yes1999-02-282019-02-28Us
US6176442Yes1996-12-012016-12-01Us
US7837235Yes2008-09-132028-09-13Us
US5964416Yes1997-04-042017-04-04Us
US7284474Yes2005-02-262025-02-26Us
US6977042Yes1999-02-282019-02-28Us
US6988496Yes2000-08-232020-08-23Us
US8044046No2003-11-102023-11-10Us
US8034809No2005-05-122025-05-12Us
US7220742No2005-05-122025-05-12Us
US7491719No2003-11-102023-11-10Us
US7056916No2003-12-072023-12-07Us
US7727984No2003-11-102023-11-10Us
US7786111No2003-11-102023-11-10Us
US9010323No2010-04-192030-04-19Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0156 mg/mLALOGPS
logP-0.55ALOGPS
logP-1.8ChemAxon
logS-4.4ALOGPS
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
Human
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
Human
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
Human
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
Human
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
Human
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
Human
Pharmacological action
Unknown
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
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
Human
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 21, 2018 00:22