IPRATROPIUM BROMIDE ANHYDROUS

First approved in 1986

Details

Stereochemistry	RACEMIC
Molecular Formula	C20H30NO3.Br
Molecular Weight	412.361
Optical Activity	( + / - )
Defined Stereocenters	3 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of IPRATROPIUM BROMIDE ANHYDROUS

Structure Search

SMILES

[Br-].CC(C)[N@+]1(C)[C@H]2CC[C@@H]1C[C@@H](C2)OC(=O)C(CO)C3=CC=CC=C3

InChI

InChIKey=LHLMOSXCXGLMMN-WDTICOSOSA-M

InChI=1S/C20H30NO3.BrH/c1-14(2)21(3)16-9-10-17(21)12-18(11-16)24-20(23)19(13-22)15-7-5-4-6-8-15;/h4-8,14,16-19,22H,9-13H2,1-3H3;1H/q+1;/p-1/t16-,17+,18+,19?,21?;

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021527s021lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/68009241

Ipratropium (ipratropium bromide, ATROVENT® HFA) is a muscarinic antagonist structurally related to atropine but often considered safer and more effective for inhalation use. It is indicated for the maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Ipratropium (ipratropium bromide, ATROVENT® HFA) is an anticholinergic (parasympatholytic) agent which, based on animal studies, appears to inhibit vagally-mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released at the neuromuscular junctions in the lung. Anticholinergics prevent the increases in intracellular concentration of Ca2+ which is caused by interaction of acetylcholine with the muscarinic receptors on bronchial smooth muscle.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL216 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021527s021lbl.pdf	Antagonist 2778	0.49 nM [Ki]
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021527s021lbl.pdf	Antagonist 2778	1.5 nM [Ki]
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021527s021lbl.pdf	Antagonist 2778	0.51 nM [Ki]
Muscarinic acetylcholine receptor M4 86 Target ID: CHEMBL1821 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021527s021lbl.pdf	Antagonist 2778	0.66 nM [Ki]
Muscarinic acetylcholine receptor M5 62 Target ID: CHEMBL2035 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021527s021lbl.pdf	Antagonist 2778	1.7 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic obstructive pulmonary disease 174 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021527s021lbl.pdf	Primary		Approved 8429	ATROVENT HFA Approved Use ATROVENT HFA Inhalation Aerosol is indicated as a bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Launch Date 2004

C_max

Value	Dose	Co-administered	Analyte	Population
33.5 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021747s010lbl.pdf	20 μg 4 times / day multiple, respiratory dose: 20 μg route of administration: Respiratory experiment type: MULTIPLE co-administered: ALBUTEROL	ALBUTEROL	IPRATROPIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
31.7 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021747s010lbl.pdf	20 μg 4 times / day steady-state, respiratory dose: 20 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered: ALBUTEROL	ALBUTEROL	IPRATROPIUM plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN
35.4 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021747s010lbl.pdf	20 μg 4 times / day steady-state, respiratory dose: 20 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered: ALBUTEROL	ALBUTEROL	IPRATROPIUM plasma	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1.04 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021747s010lbl.pdf	20 μg 4 times / day multiple, respiratory dose: 20 μg route of administration: Respiratory experiment type: MULTIPLE co-administered: ALBUTEROL	ALBUTEROL	IPRATROPIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
123 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021747s010lbl.pdf	20 μg 4 times / day steady-state, respiratory dose: 20 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered: ALBUTEROL	ALBUTEROL	IPRATROPIUM plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN
131 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021747s010lbl.pdf	20 μg 4 times / day steady-state, respiratory dose: 20 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered: ALBUTEROL	ALBUTEROL	IPRATROPIUM plasma	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021747s010lbl.pdf	20 μg 4 times / day multiple, respiratory dose: 20 μg route of administration: Respiratory experiment type: MULTIPLE co-administered: ALBUTEROL	ALBUTEROL	IPRATROPIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
95.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021747s010lbl.pdf	20 μg 4 times / day multiple, respiratory dose: 20 μg route of administration: Respiratory experiment type: MULTIPLE co-administered: ALBUTEROL	ALBUTEROL	IPRATROPIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
168 ug 3 times / day steady, respiratory Highest studied dose Dose: 168 ug, 3 times / day Route: respiratory Route: steady Dose: 168 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7751529/	unhealthy, 18 - 75 years n = 96 Health Status: unhealthy Condition: perennial allergic rhinitis Age Group: 18 - 75 years Sex: M+F Population Size: 96 Sources: https://pubmed.ncbi.nlm.nih.gov/7751529/	Disc. AE: Nasal disorder NOS, Nasal dryness... AEs leading to discontinuation/dose reduction: Nasal disorder NOS (17%) Nasal dryness (2%) Epistaxis (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/7751529/
168 ug 3 times / day steady, respiratory Highest studied dose Dose: 168 ug, 3 times / day Route: respiratory Route: steady Dose: 168 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/	unhealthy, 2 - 5 years n = 43 Health Status: unhealthy Condition: common colds Age Group: 2 - 5 years Sex: M+F Population Size: 43 Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/	Disc. AE: Epistaxis... AEs leading to discontinuation/dose reduction: Epistaxis (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/
84 ug 3 times / day steady, respiratory Highest studied dose Dose: 84 ug, 3 times / day Route: respiratory Route: steady Dose: 84 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/	unhealthy, 2 - 5 years n = 187 Health Status: unhealthy Condition: allergies Age Group: 2 - 5 years Sex: M+F Population Size: 187 Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/	Disc. AE: Epistaxis, Upper respiratory tract infection... AEs leading to discontinuation/dose reduction: Epistaxis (1 patient) Upper respiratory tract infection (1 patient) Ear infection (1 patient) Exacerbation of asthma (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/
200 ug single, respiratory Highest studied dose Dose: 200 ug Route: respiratory Route: single Dose: 200 ug Sources: https://pubmed.ncbi.nlm.nih.gov/2150695/	unhealthy, mean 40.7 years n = 20 Health Status: unhealthy Condition: stable chronic asthma Age Group: mean 40.7 years Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/2150695/	Disc. AE: Nausea and vomiting... AEs leading to discontinuation/dose reduction: Nausea and vomiting (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/2150695/
42 ug 1 times / day steady, respiratory Recommended Dose: 42 ug, 1 times / day Route: respiratory Route: steady Dose: 42 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7751528/	unhealthy, mean 42.6 years n = 99 Health Status: unhealthy Condition: rhinorrhea Age Group: mean 42.6 years Sex: M+F Population Size: 99 Sources: https://pubmed.ncbi.nlm.nih.gov/7751528/	Other AEs: Nasal disorder NOS... Other AEs: Nasal disorder NOS (19 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/7751528/

AEs

AE	Significance	Dose	Population
Nasal disorder NOS	17% Disc. AE	168 ug 3 times / day steady, respiratory Highest studied dose Dose: 168 ug, 3 times / day Route: respiratory Route: steady Dose: 168 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7751529/	unhealthy, 18 - 75 years n = 96 Health Status: unhealthy Condition: perennial allergic rhinitis Age Group: 18 - 75 years Sex: M+F Population Size: 96 Sources: https://pubmed.ncbi.nlm.nih.gov/7751529/
Epistaxis	2% Disc. AE	168 ug 3 times / day steady, respiratory Highest studied dose Dose: 168 ug, 3 times / day Route: respiratory Route: steady Dose: 168 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7751529/	unhealthy, 18 - 75 years n = 96 Health Status: unhealthy Condition: perennial allergic rhinitis Age Group: 18 - 75 years Sex: M+F Population Size: 96 Sources: https://pubmed.ncbi.nlm.nih.gov/7751529/
Nasal dryness	2% Disc. AE	168 ug 3 times / day steady, respiratory Highest studied dose Dose: 168 ug, 3 times / day Route: respiratory Route: steady Dose: 168 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7751529/	unhealthy, 18 - 75 years n = 96 Health Status: unhealthy Condition: perennial allergic rhinitis Age Group: 18 - 75 years Sex: M+F Population Size: 96 Sources: https://pubmed.ncbi.nlm.nih.gov/7751529/
Epistaxis	1 patient Disc. AE	168 ug 3 times / day steady, respiratory Highest studied dose Dose: 168 ug, 3 times / day Route: respiratory Route: steady Dose: 168 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/	unhealthy, 2 - 5 years n = 43 Health Status: unhealthy Condition: common colds Age Group: 2 - 5 years Sex: M+F Population Size: 43 Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/
Ear infection	1 patient Disc. AE	84 ug 3 times / day steady, respiratory Highest studied dose Dose: 84 ug, 3 times / day Route: respiratory Route: steady Dose: 84 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/	unhealthy, 2 - 5 years n = 187 Health Status: unhealthy Condition: allergies Age Group: 2 - 5 years Sex: M+F Population Size: 187 Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/
Epistaxis	1 patient Disc. AE	84 ug 3 times / day steady, respiratory Highest studied dose Dose: 84 ug, 3 times / day Route: respiratory Route: steady Dose: 84 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/	unhealthy, 2 - 5 years n = 187 Health Status: unhealthy Condition: allergies Age Group: 2 - 5 years Sex: M+F Population Size: 187 Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/
Exacerbation of asthma	1 patient Disc. AE	84 ug 3 times / day steady, respiratory Highest studied dose Dose: 84 ug, 3 times / day Route: respiratory Route: steady Dose: 84 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/	unhealthy, 2 - 5 years n = 187 Health Status: unhealthy Condition: allergies Age Group: 2 - 5 years Sex: M+F Population Size: 187 Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/
Upper respiratory tract infection	1 patient Disc. AE	84 ug 3 times / day steady, respiratory Highest studied dose Dose: 84 ug, 3 times / day Route: respiratory Route: steady Dose: 84 ug, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/	unhealthy, 2 - 5 years n = 187 Health Status: unhealthy Condition: allergies Age Group: 2 - 5 years Sex: M+F Population Size: 187 Sources: https://pubmed.ncbi.nlm.nih.gov/15702820/
Nausea and vomiting	1 patient Disc. AE	200 ug single, respiratory Highest studied dose Dose: 200 ug Route: respiratory Route: single Dose: 200 ug Sources: https://pubmed.ncbi.nlm.nih.gov/2150695/	unhealthy, mean 40.7 years n = 20 Health Status: unhealthy Condition: stable chronic asthma Age Group: mean 40.7 years Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/2150695/
Nasal disorder NOS	19 patients	42 ug 1 times / day steady, respiratory Recommended Dose: 42 ug, 1 times / day Route: respiratory Route: steady Dose: 42 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7751528/	unhealthy, mean 42.6 years n = 99 Health Status: unhealthy Condition: rhinorrhea Age Group: mean 42.6 years Sex: M+F Population Size: 99 Sources: https://pubmed.ncbi.nlm.nih.gov/7751528/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 512 OCT2 647 OCT3 150 MATE1 306 MATE2 263	OCTN1 47 OCTN2 50 OCT1 327 OCT2 355 OCT3 80 MATE1 135 MATE2 96

Drug as perpetrator

Target	Modality	Activity
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/27676604/ Page: 6,21	yes [IC50 17.4 uM]
OCT3 150	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/27676604/ Page: 6,21	yes [IC50 2.5 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/27676604/ Page: 6,21	yes [IC50 3.6 uM]
MATE1 308	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/27676604/ Page: 6,21	yes [IC50 30.5 uM]
MATE2 263	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/27676604/ Page: 6,21	yes [IC50 62.8 uM]

Drug as victim

Target	Modality	Activity
MATE1 135	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27676604/ Page: 7,21	strong
MATE2 96	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27676604/ Page: 7,21	strong
OCT1 327	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27676604/ Page: 7,21	strong
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27676604/ Page: 7,21	strong
OCT3 80	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27676604/ Page: 7,21	strong
OCTN1 47	substrate 3367 Sources: https://pubs.acs.org/doi/10.1021/mp900206j	yes
OCTN2 50	substrate 3367 Sources: https://pubs.acs.org/doi/10.1021/mp900206j	yes

Sourcing

Vendor/Aggregator	ID	URL
KeyOrganics	KS-5051
Pharmeks	PHAR218016
ZINC	ZINC000013782937	http://zinc15.docking.org/substances/ZINC000013782937

PubMed

Title	Date	PubMed
Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants.	2001	11687053
Clinical prescribing of allergic rhinitis medication in the preschool and young school-age child: what are the options?	2001	11520256
Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease.	2001 Apr	11316640
The role of domiciliary nebulizers in managing patients with severe COPD.	2001 Apr	11316108
Tiotropium bromide.	2001 Apr	11281822
Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease.	2001 Jan	11208630
Analyses of quaternary ammonium drugs in horse urine by capillary electrophoresis-mass spectrometry.	2001 Jul	11504053
Effectiveness of salmeterol versus ipratropium bromide on exertional dyspnoea in COPD.	2001 Jun	11491155
Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Salbutamol and ipratropium in COPD.	2001 Mar	11300184
Function of pulmonary neuronal M(2) muscarinic receptors in stable chronic obstructive pulmonary disease.	2001 May	11371395
Effects of inhalation of albuterol sulphate, ipratroprium bromide and frusemide on breathing mechanics and gas exchange in healthy exercising horses.	2001 May	11352354
Ipratropium bromide hydrofluoroalkane inhalation aerosol is safe and effective in patients with COPD.	2001 Oct	11591569
Posttraumatic pseudo-cerebrospinal fluid rhinorrhea.	2001 Sep	11568683
[Effect of anticholinergic therapy on myocardial reserve dynamics in patients with chronic obstructive bronchitis].	2001 Sep-Dec	11881364
[Pharmacodynamics of inhalation broncholytic agents introduced in a single dose by nebulizer in patients with severe exacerbation of bronchial asthma].	2002	11980113
Pressurised metered-dose inhalers versus all other hand-held inhalers devices to deliver bronchodilators for chronic obstructive pulmonary disease.	2002	11869627
Pharmacodynamic steady state of tiotropium in patients with chronic obstructive pulmonary disease.	2002 Apr	11998992
Clinical review: severe asthma.	2002 Feb	11940264
Mydriasis due to self-administered inhaled ipratropium bromide.	2002 Mar	11998922

Patents

Sample Use Guides

In Vivo Use Guide

The usual starting dose of ATROVENT® HFA is two inhalations four times a day. Patients may take additional inhalations as required; however, the total number of inhalations should not exceed 12 in 24 hours.

Route of Administration: Oral

In Vitro Use Guide

Ba 679 BR, atropine, and ipratropium bromide inhibited electrical field stimulation (EFS)-induced contraction with IC50 values of 0.17, 0.74, and 0.58 nM, respectively, in guinea pig trachea. Ba 679 BR had a slower onset and longer duration of action than atropine or ipratropium bromide (the times required to attain 50% of the maximum response were 34.8, 3.8, and 7.6 min, respectively, and the times required for 50% recovery of the response were 540, 31.6, and 81.2 min, respectively).

Name

Type

Language

IPRATROPIUM BROMIDE ANHYDROUS

Common Name

English

IPRATROPIUM BROMIDE [MI]

Common Name

English

ipratropium bromide [INN]

Common Name

English

Ipratropium bromide [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

R01AX03