Anisotropine methylbromide

Identification

Name
Anisotropine methylbromide
Accession Number
DB00517  (APRD00800)
Type
Small Molecule
Groups
Approved
Description

Anisotropine methylbromide is a quaternary ammonium compound. Its use as treatment adjunct in peptic ulcer has been replaced by the use of more effective agents. Depending on the dose, anisotropine methylbromide may reduce the motility and secretory activity of the gastrointestinal system, and the tone of the ureter and urinary bladder and may have a slight relaxant action on the bile ducts and gallbladder. In general, smaller doses of anisotropine methylbromide inhibit salivary and bronchial secretions, sweating, and accommodation; cause dilatation of the pupil; and increase the heart rate. Larger doses are required to decrease motility of the gastrointestinal and urinary tracts and to inhibit gastric acid secretion.

Structure
Thumb
Synonyms
  • 8-Methyl-3-(2-propylpentanoyloxy)tropinium bromide
  • 8-Methyltropinium bromide 2-propylpentanoate
  • 8-Methyltropinium bromide 2-propylvalerate
  • Anisotropine methobromide
  • Anisotropine methylbromide
  • endo-8,8-Dimethyl-3-((1-oxo-2-propylpentyl)oxy)-8-azoniabicyclo(3.2.1)octane bromide
  • Méthylbromure d'octatropine
  • Methyloctatropine bromide
  • Metilbromuro de octatropina
  • Octatropine methylbromide
  • Octatropini methylbromidum
International/Other Brands
Endovalpin / Lytispasm / Valpin (Endo)
Categories
UNII
62M960DHIL
CAS number
80-50-2
Weight
Average: 362.345
Monoisotopic: 361.16164192
Chemical Formula
C17H32BrNO2
InChI Key
QSFKGMJOKUZAJM-UHFFFAOYSA-M
InChI
InChI=1S/C17H32NO2.BrH/c1-5-7-13(8-6-2)17(19)20-16-11-14-9-10-15(12-16)18(14,3)4;/h13-16H,5-12H2,1-4H3;1H/q+1;/p-1
IUPAC Name
8,8-dimethyl-3-[(2-propylpentanoyl)oxy]-8-azabicyclo[3.2.1]octan-8-ium bromide
SMILES
[Br-].CCCC(CCC)C(=O)O[C@H]1CC2CCC(C1)[N+]2(C)C

Pharmacology

Indication

For use in conjunction with antacids or histamine H2-receptor antagonists in the treatment of peptic ulcer, to reduce further gastric acid secretion and delay gastric emptying.

Pharmacodynamics

Anisotropine methylbromide is a quaternary ammonium compound. Its use as treatment adjunct in peptic ulcer has been replaced by the use of more effective agents. Depending on the dose, anisotropine methylbromide may reduce the motility and secretory activity of the gastrointestinal system, and the tone of the ureter and urinary bladder and may have a slight relaxant action on the bile ducts and gallbladder. In general, smaller doses of anisotropine methylbromide inhibit salivary and bronchial secretions, sweating, and accommodation; cause dilatation of the pupil; and increase the heart rate. Larger doses are required to decrease motility of the gastrointestinal and urinary tracts and to inhibit gastric acid secretion.

Mechanism of action

Quaternary ammonium compounds such as anisotropine methylbromide inhibit the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves as well as on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These postganglionic receptor sites are present in the autonomic effector cells of the smooth muscle, cardiac muscle, sinoatrial and atrioventricular nodes, and exocrine glands.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M1
antagonist
Human
AMuscarinic acetylcholine receptor M2
antagonist
Human
AMuscarinic acetylcholine receptor M3
antagonist
Human
Absorption

Gastrointestinal absorption is poor and irregular. Total absorption after an oral dose is about 10 to 25%.

Volume of distribution
Not Available
Protein binding

Not Known

Metabolism

Hepatic, by enzymatic hydrolysis.

Route of elimination
Not Available
Half life

Not Known

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

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Anisotropine Methylbromide 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 Anisotropine Methylbromide is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of Tachycardia can be increased when Anisotropine Methylbromide is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of Tachycardia can be increased when Anisotropine Methylbromide is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of Tachycardia can be increased when Anisotropine Methylbromide is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of Tachycardia can be increased when Anisotropine Methylbromide is combined with 4-Methoxyamphetamine.
AbediterolThe risk or severity of Tachycardia can be increased when Anisotropine Methylbromide is combined with Abediterol.
AcebutololThe risk or severity of Tachycardia can be increased when Anisotropine Methylbromide is combined with Acebutolol.
AclidiniumThe risk or severity of adverse effects can be increased when Anisotropine Methylbromide is combined with Aclidinium.
AdenosineThe risk or severity of Tachycardia can be increased when Anisotropine Methylbromide is combined with Adenosine.
Food Interactions
Not Available

References

Synthesis Reference

Weiner, N. and Gordon, S.M.; US. Patent 2,962,499; November 29,1960; assigned to Endo Laboratories, Inc.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014658
KEGG Drug
D00232
KEGG Compound
C06830
PubChem Compound
21867154
PubChem Substance
46504810
ChemSpider
10611962
ChEBI
2739
ChEMBL
CHEMBL1578
Therapeutic Targets Database
DAP000837
PharmGKB
PA164754880
Wikipedia
Anisotropine_Methylbromide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Watson laboratories inc
  • Endo pharmaceuticals inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)329 °CWeiner, N. and Gordon, S.M.; US. Patent 2,962,499; November 29,1960; assigned to Endo Laboratories, Inc.
water solubility1600 mg/LNot Available
logP0.60Not Available
Predicted Properties
PropertyValueSource
Water Solubility9.67e-05 mg/mLALOGPS
logP-0.4ALOGPS
logP-0.67ChemAxon
logS-6.6ALOGPS
pKa (Strongest Basic)-7.1ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area26.3 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity93.26 m3·mol-1ChemAxon
Polarizability34.09 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7332
Blood Brain Barrier+0.9683
Caco-2 permeable+0.602
P-glycoprotein substrateNon-substrate0.5078
P-glycoprotein inhibitor INon-inhibitor0.6258
P-glycoprotein inhibitor IINon-inhibitor0.8571
Renal organic cation transporterNon-inhibitor0.5586
CYP450 2C9 substrateNon-substrate0.8222
CYP450 2D6 substrateNon-substrate0.7474
CYP450 3A4 substrateSubstrate0.6949
CYP450 1A2 substrateNon-inhibitor0.7455
CYP450 2C9 inhibitorNon-inhibitor0.8657
CYP450 2D6 inhibitorNon-inhibitor0.7622
CYP450 2C19 inhibitorNon-inhibitor0.8572
CYP450 3A4 inhibitorNon-inhibitor0.937
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9752
Ames testNon AMES toxic0.7025
CarcinogenicityNon-carcinogens0.8765
BiodegradationReady biodegradable0.8093
Rat acute toxicity2.6936 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9113
hERG inhibition (predictor II)Non-inhibitor0.7206
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
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tropane alkaloids. These are organic compounds containing the nitrogenous bicyclic alkaloid parent N-Methyl-8-azabicyclo[3.2.1]octane.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Tropane alkaloids
Sub Class
Not Available
Direct Parent
Tropane alkaloids
Alternative Parents
Fatty acid esters / Piperidines / N-alkylpyrrolidines / Tetraalkylammonium salts / Carboxylic acid esters / Monocarboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Organic bromide salts
show 3 more
Substituents
Tropane alkaloid / Fatty acid ester / Piperidine / N-alkylpyrrolidine / Fatty acyl / Pyrrolidine / Tetraalkylammonium salt / Quaternary ammonium salt / Carboxylic acid ester / Carboxylic acid derivative
show 15 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
quaternary ammonium salt, organic bromide salt (CHEBI:2739)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Bachrach WH: Clinical evaluation of anisotropine methyl bromide (valpin), an anticholinergic drug. Am J Dig Dis. 1972 Jun;17(6):505-12. [PubMed:4555460]
  4. Tittor W, Lechmann R, Herrmann HJ, Dincer T, Weckesser G: [Effectiveness of octatropine methylbromide (OMB) in the treatment of gastritis, duodenal ulcer and spastic colon--a double blind study]. ZFA (Stuttgart). 1982 Sep 30;58(27):1481-4. [PubMed:6897316]
  5. Pace F, Maurano A, Ciacci C, Savarino V, Attili A, Iaquinto G, Magni E, Porro GB: Octatropine methyl bromide and diazepam combination (Valpinax) in patients with irritable bowel syndrome: a multicentre, randomized, placebo-controlled trial. Eur Rev Med Pharmacol Sci. 2010 Mar;14(3):155-62. [PubMed:20391952]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Bachrach WH: Clinical evaluation of anisotropine methyl bromide (valpin), an anticholinergic drug. Am J Dig Dis. 1972 Jun;17(6):505-12. [PubMed:4555460]
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Bachrach WH: Clinical evaluation of anisotropine methyl bromide (valpin), an anticholinergic drug. Am J Dig Dis. 1972 Jun;17(6):505-12. [PubMed:4555460]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 15:11