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Identification
Name Ipratropium bromide
Accession Number DB00332 (APRD00537)
Type small molecule
Groups approved
Description

A muscarinic antagonist structurally related to atropine but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Ipatropium Bromide
  • ipratropium
  • N-Isopropylatropine
Synonyms
Ipatropium Bromide
ipratropium
N-Isopropylatropine
Salts Not Available
Brand names
Name Company
Aerodose
Aerovent
Apo-Ipravent
Apovent
Atronase
Atrovent
Atrovent Aerosol
Atrovent HFA
Atrovent Nasal
Bitrop
Disne-Asmol
Ipravent
Ipvent
Kendral-Ipratropium
Narilet
Rhinotrop
Rhinovent
Rinatec
Rinoberen
Rinovagos
Vagos
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Brand mixtures
Brand Name Ingredients
Combivent Inhalation Aerosol Ipratropium Bromide + Salbutamol Sulfate
Combivent Inhalation Solution Ipratropium Bromide + Salbutamol Sulfate
Duovent UDV Fenoterol Hydrobromide + Ipratropium Bromide
Ratio-Ipra SAL UDV Ipratropium Bromide + Salbutamol Sulfate
Categories
  • Bronchodilator Agents
  • Antispasmodics
  • Cholinergic Antagonists
  • Antimuscarinics
CAS number 60205-81-4
Weight Average: 412.361
Monoisotopic: 411.140906478
Chemical Formula C20H30BrNO3
InChI Key InChIKey=LHLMOSXCXGLMMN-VVQPYUEFSA-M
InChI
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+;
Plain Text
IUPAC Name
(1R,3R,5S,8R)-3-[(3-hydroxy-2-phenylpropanoyl)oxy]-8-methyl-8-(propan-2-yl)-8-azabicyclo[3.2.1]octan-8-ium bromide
SMILES
[Br-].[H][C@]12CC[C@]([H])(C[C@@H](C1)OC(=O)C(CO)C1=CC=CC=C1)[N@+]2(C)C(C)C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema.
Pharmacodynamics Ipratropium bromide, a synthetic ammonium compound structurally similar to atropine, is used as a bronchodilator in the management of cholinergic-mediated bronchospasm associated with chronic obstructive pulmonary disease and in the treatment of rhinorrhea associated with the common cold or with allergic or nonallergic seasonal rhinitis.
Mechanism of action Ipratropium bromide is an anticholinergic agent. It blocks muscarinic cholinergic receptors, without specificity for subtypes, resulting in a decrease in the formation of cyclic guanosine monophosphate (cGMP). Most likely due to actions of cGMP on intracellular calcium, this results in decreased contractility of smooth muscle.
Absorption Inhalation (local)-minimal; Nasal-rapid and minimal
Volume of distribution
  • 4.6 L/kg
Protein binding Minimally (0 to 9% in vitro) bound to plasma albumin and α1-acid glycoproteins
Metabolism Partially metabolized to at least 8 metabolites formed primarily via hydrolysis and conjugation. The main metabolites are N-isopropylnortropium methobromide, which is formed by enzymatic hydrolysis of the ester; α-phenylacrylic acid-N-isopropylnortropine-ester methobromide, which is formed by enzymatic loss of a water; and phenylacetic acid-N-isopropylnortropine-ester methobromide, which is formed by enzymatic loss of a CH3OH-group. These metabolites appear to be inactive.
Route of elimination Primarily eliminated renally via active secretion.
Half life 2-4 hours after administration orally, IV or by oral inhalation (radiolabeled ipratropium bromide assay measures parent drug and its metabolites). Using a radioreceptor assay that measures only unchanged ipratropium bromide, the initial distribution-phase half-life (t1/2 α) and terminal elimination-phase half-life (t1/2 β) were 0.07 and 1.6 hours, respectively, following a single 2 mg IV dose of the drug in healthy adults.
Clearance
  • 2.3 L/min (total clearance of active ingredient)
Toxicity LD50=1001mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Boehringer ingelheim pharmaceuticals inc
  • Actavis mid atlantic llc
  • Bausch and lomb pharmaceuticals inc
  • Cobalt laboratories inc
  • Dey lp
  • Holopack international corp
  • Landela pharmaceutical
  • Nephron corp
  • Novex pharma
  • Pharmascience inc
  • Roxane laboratories inc
  • Teva parenteral medicines inc
  • Bausch and lomb inc
Packagers
Dosage forms
Form Route Strength
Aerosol, metered Nasal 21 mcg, 42 mcg
Solution Respiratory (inhalation) 0.0125%, 0.02%, 0.025%
Spray, metered Nasal 17 mcg, 20 mcg
Prices
Unit description Cost Unit
Atrovent HFA 17 mcg/act Aerosol 12.9 gm Inhaler 143.59 USD inhaler
Ipratropium bromide powder 100.06 USD g
Atrovent 0.03% Solution 30ml Nasal Spray 96.95 USD bottle
Atrovent 0.06% Solution 15ml Nasal Spray 84.68 USD bottle
Ipratropium Bromide 0.03% Solution 30ml Bottle 53.82 USD bottle
Ipratropium Bromide 0.06% Solution 15ml Bottle 46.14 USD bottle
Ipratropium Bromide 0.02% Solution Each Box Contains Twenty-Five 2.5ml Vials 45.86 USD box
Atrovent hfa inhaler 11.89 USD g
Atrovent 0.06% spray 5.33 USD ml
Atrovent 0.03% spray 3.11 USD ml
Ipratropium 0.06% spray 2.96 USD ml
Ipratropium 0.03% spray 1.73 USD ml
Atrovent 0.03 % Spray 1.04 USD ml
Apo-Ipravent 250 mcg/ml Solution 0.58 USD ml
Mylan-Ipratropium 250 mcg/ml Solution 0.58 USD ml
Novo-Ipramide 250 mcg/ml Solution 0.58 USD ml
Pms-Ipratropium 0.03 % Spray 0.58 USD ml
Pms-Ipratropium 250 mcg/ml Solution 0.58 USD ml
Atrovent Hfa 20 mcg/dose Metered Dose Aerosol 0.1 USD metered dose aerosol
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Patents
Country Patent Number Approved Expires (estimated)
United States 6739333 2000-05-26 2020-05-26
United States 5766573 1992-11-28 2009-11-28
Canada 2151383 2005-02-08 2013-12-06
Properties
State solid
Melting point 230-232oC
Experimental Properties
Property Value Source
water solubility Freely soluble PhysProp
Predicted Properties
Property Value Source
water solubility 7.01e-04 g/l ALOGPS
logP 0.21 ALOGPS
logP -1.8 ChemAxon Molconvert
logS -5.8 ALOGPS
pKa 0 ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 46.53 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 105.9 ChemAxon Molconvert
polarizability 37.43 ChemAxon Molconvert
References
Synthesis Reference
  1. Abdine HH, Belala F, and Al-Badra AA. (2003). Ipratropium bromide: Methods of chemical and biochemical synthesis. In H.G. Brittain (Ed.). Profiles of drug substances, excipients and related methodology (pp. 85-99). Amsterdam, Netherlands: Elsevier Academic Press.
General Reference
  1. Yamatake Y, Sasagawa S, Yanaura S, Okamiya Y: [Antiallergic asthma effect of ipatropium bromide (Sch 1000) in dogs (author’s transl)] Nippon Yakurigaku Zasshi. 1977 Oct;73(7):785-91. Pubmed
External Links
Resource Link
KEGG Compound C07052 Link_out
ChEBI 46659 Link_out
ChEMBL 46659 Link_out
Therapeutic Targets Database DNC000806 Link_out
PharmGKB PA450082 Link_out
IUPHAR 325 Link_out
Guide to Pharmacology 325 Link_out
Drug Product Database 2240072 Link_out
RxList http://www.rxlist.com/cgi/generic/ipratrop.htm Link_out
Drugs.com http://www.drugs.com/mtm/ipratropium-nasal.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Ipratropium Link_out
ATC Codes
  • R01AX03
  • R03BB01
AHFS Codes
  • 12:08.08
PDB Entries Not Available
FDA label show (88.1 KB)
MSDS show (72.7 KB)
Interactions
Drug Interactions
Drug Interaction
Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Ipratropium, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Trimethobenzamide Trimethobenzamide and Ipratropium, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Triprolidine Triprolidine and Ipratropium, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Trospium Trospium and Ipratropium, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food Interactions Not Available
Targets

1. Muscarinic acetylcholine receptor M1

Pharmacological action: yes
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P11229 Link_out
Gene: CHRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wellington K: Ipratropium bromide HFA. Treat Respir Med. 2005;4(3):215-20; discussion 221-2. Pubmed

2. Muscarinic acetylcholine receptor M2

Pharmacological action: yes
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition

Organism class: human
UniProt ID: P08172 Link_out
Gene: CHRM2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wellington K: Ipratropium bromide HFA. Treat Respir Med. 2005;4(3):215-20; discussion 221-2. Pubmed

3. Muscarinic acetylcholine receptor M3

Pharmacological action: yes
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P20309 Link_out
Gene: CHRM3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wellington K: Ipratropium bromide HFA. Treat Respir Med. 2005;4(3):215-20; discussion 221-2. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: substrate

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Cytochrome P450 3A4

Actions: substrate

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Organic cation/carnitine transporter 2

Actions: substrate

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 cations such as tetraethylammonium (TEA) without the involvement of sodium. Also Relative uptake activity ratio of carnitine to TEA is 11.3

UniProt ID: O76082 Link_out
Gene: SLC22A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed

2. Organic cation/carnitine transporter 1

Actions: substrate

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 the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET)

UniProt ID: Q9H015 Link_out
Gene: SLC22A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2012 13:11