Identification

Name
Methacholine
Accession Number
DB06709
Type
Small Molecule
Groups
Approved, Investigational
Description

Methacholine acts as a non-selective muscarinic receptor agonist to stimulate the parasympathetic nervous system. It is most commonly used for diagnosing bronchial hyperreactivity, using the bronchial challenge test. Through this test, the drug causes bronchoconstriction and people with pre-existing airway hyperreactivity, such as asthmatics, will react to lower doses of drug.

Structure
Thumb
Synonyms
  • Acetyl-beta-methylcholine
  • Acetylmethylcholine
  • MCh
  • Methacholine
Product Ingredients
IngredientUNIICASInChI Key
Methacholine chloride0W5ETF9M2K62-51-1JHPHVAVFUYTVCL-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Methacholine Chloride, USPPowder, for solution1600 mgRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada
Methacholine Chloride, USPPowder, for solution320 mgRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada
Methacholine Chloride, USPPowder, for solution160 mgRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada
Methacholine Chloride, USPPowder, for solution1280 mgRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada
Methacholine Chloride, USPPowder, for solution100 mgRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada
Methacholine OmegaPowder, for solution480 mgRespiratory (inhalation)Omega Laboratories Ltd2006-03-21Not applicableCanada
Methacholine OmegaPowder, for solution1600 mgRespiratory (inhalation)Omega Laboratories Ltd2006-07-03Not applicableCanada
Methacholine OmegaPowder, for solution100 mgRespiratory (inhalation)Omega Laboratories Ltd2006-03-27Not applicableCanada
ProvocholinePowder, for solution320 mgRespiratory (inhalation)Methapharm, Inc.2003-03-12Not applicableCanada
ProvocholinePowder, for solution100 mgRespiratory (inhalation)Methapharm, Inc.1999-04-01Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Sterile Provocholine SolutionMethacholine chloride (0.0625 mg) + Methacholine chloride (0.25 mg) + Methacholine chloride (1 mg) + Methacholine chloride (16 mg) + Methacholine chloride (4 mg)SolutionRespiratory (inhalation)Methapharm, Inc.Not applicableNot applicableCanada
Sterile Provocholine SolutionMethacholine chloride (0.0625 mg) + Methacholine chloride (0.25 mg) + Methacholine chloride (1 mg) + Methacholine chloride (16 mg) + Methacholine chloride (4 mg)SolutionRespiratory (inhalation)Methapharm, Inc.Not applicableNot applicableCanada
Sterile Provocholine SolutionMethacholine chloride (0.0625 mg) + Methacholine chloride (0.25 mg) + Methacholine chloride (1 mg) + Methacholine chloride (16 mg) + Methacholine chloride (4 mg)SolutionRespiratory (inhalation)Methapharm, Inc.Not applicableNot applicableCanada
Sterile Provocholine SolutionMethacholine chloride (0.0625 mg) + Methacholine chloride (0.25 mg) + Methacholine chloride (1 mg) + Methacholine chloride (16 mg) + Methacholine chloride (4 mg)SolutionRespiratory (inhalation)Methapharm, Inc.Not applicableNot applicableCanada
Sterile Provocholine SolutionMethacholine chloride (0.0625 mg) + Methacholine chloride (0.25 mg) + Methacholine chloride (1 mg) + Methacholine chloride (16 mg) + Methacholine chloride (4 mg)SolutionRespiratory (inhalation)Methapharm, Inc.Not applicableNot applicableCanada
Sterile Provocholine Solution PlusMethacholine chloride (0.0625 mg) + Methacholine chloride (0.125 mg) + Methacholine chloride (0.25 mg) + Methacholine chloride (0.50 mg) + Methacholine chloride (1 mg) + Methacholine chloride (16 mg) + Methacholine chloride (2 mg) + Methacholine chloride (4 mg) + Methacholine chloride (8 mg)SolutionRespiratory (inhalation)Methapharm, Inc.Not applicableNot applicableCanada
Sterile Provocholine Solution PlusMethacholine chloride (0.0625 mg) + Methacholine chloride (0.125 mg) + Methacholine chloride (0.25 mg) + Methacholine chloride (0.50 mg) + Methacholine chloride (1 mg) + Methacholine chloride (16 mg) + Methacholine chloride (2 mg) + Methacholine chloride (4 mg) + Methacholine chloride (8 mg)SolutionRespiratory (inhalation)Methapharm, Inc.Not applicableNot applicableCanada
Sterile Provocholine Solution PlusMethacholine chloride (0.0625 mg) + Methacholine chloride (0.125 mg) + Methacholine chloride (0.25 mg) + Methacholine chloride (0.50 mg) + Methacholine chloride (1 mg) + Methacholine chloride (16 mg) + Methacholine chloride (2 mg) + Methacholine chloride (4 mg) + Methacholine chloride (8 mg)SolutionRespiratory (inhalation)Methapharm, Inc.Not applicableNot applicableCanada
Sterile Provocholine Solution PlusMethacholine chloride (0.0625 mg) + Methacholine chloride (0.125 mg) + Methacholine chloride (0.25 mg) + Methacholine chloride (0.50 mg) + Methacholine chloride (1 mg) + Methacholine chloride (16 mg) + Methacholine chloride (2 mg) + Methacholine chloride (4 mg) + Methacholine chloride (8 mg)SolutionRespiratory (inhalation)Methapharm, Inc.Not applicableNot applicableCanada
Sterile Provocholine Solution PlusMethacholine chloride (0.0625 mg) + Methacholine chloride (0.125 mg) + Methacholine chloride (0.25 mg) + Methacholine chloride (0.50 mg) + Methacholine chloride (1 mg) + Methacholine chloride (16 mg) + Methacholine chloride (2 mg) + Methacholine chloride (4 mg) + Methacholine chloride (8 mg)SolutionRespiratory (inhalation)Methapharm, Inc.Not applicableNot applicableCanada
Categories
UNII
03V657ZD3V
CAS number
55-92-5
Weight
Average: 160.234
Monoisotopic: 160.133753825
Chemical Formula
C8H18NO2
InChI Key
NZWOPGCLSHLLPA-UHFFFAOYSA-N
InChI
InChI=1S/C8H18NO2/c1-7(11-8(2)10)6-9(3,4)5/h7H,6H2,1-5H3/q+1
IUPAC Name
[2-(acetyloxy)propyl]trimethylazanium
SMILES
CC(C[N+](C)(C)C)OC(C)=O

Pharmacology

Indication

It is most commonly used for diagnosing bronchial hyperreactivity, using the bronchial challenge test.

Associated Conditions
Pharmacodynamics

Methacholine acts as a non-selective muscarinic receptor agonist to stimulate the parasympathetic nervous system. It is highly active at all of the muscarinic receptors

Mechanism of action

By agonizing the muscarinic receptors, this drug induces bronchoconstriction. This bronchoconstriction is used as a test in asthmatics and in bronchial hyperreactivity.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M3
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe risk or severity of adverse effects can be increased when 1,10-Phenanthroline is combined with Methacholine.
AcebutololAcebutolol may increase the bronchoconstrictory activities of Methacholine.
AlprenololAlprenolol may increase the bronchoconstrictory activities of Methacholine.
AmbenoniumThe risk or severity of adverse effects can be increased when Ambenonium is combined with Methacholine.
AmikacinThe therapeutic efficacy of Methacholine can be decreased when used in combination with Amikacin.
ArotinololArotinolol may increase the bronchoconstrictory activities of Methacholine.
AsenapineAsenapine may increase the bronchoconstrictory activities of Methacholine.
AtenololAtenolol may increase the bronchoconstrictory activities of Methacholine.
BefunololBefunolol may increase the bronchoconstrictory activities of Methacholine.
BetaxololBetaxolol may increase the bronchoconstrictory activities of Methacholine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015654
KEGG Compound
C07471
PubChem Compound
1993
PubChem Substance
99443261
ChemSpider
1916
BindingDB
48918
ChEBI
6804
ChEMBL
CHEMBL978
PharmGKB
PA165958382
Wikipedia
Methacholine
AHFS Codes
  • 36:89.00* — Other Diagnostics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAsthma Bronchial / Diabetes Mellitus (DM)1
1CompletedTreatmentHealthy Volunteers1
3CompletedDiagnosticAsthma Bronchial2
3CompletedPreventionAsthma Bronchial1
3Not Yet RecruitingOtherAsthma Bronchial1
4CompletedNot AvailableAsthma Bronchial1
4CompletedDiagnosticAsthma Bronchial1
4Not Yet RecruitingBasic ScienceAsthma Bronchial / Cough Variant Asthma / Coughing1
4RecruitingNot AvailableAsthma Bronchial1
Not AvailableActive Not RecruitingBasic ScienceAsthma Bronchial / Cough Variant Asthma1
Not AvailableCompletedBasic ScienceAsthma, Allergic1
Not AvailableCompletedDiagnosticAsthma Bronchial2
Not AvailableCompletedTreatmentAsthma Bronchial1
Not AvailableRecruitingBasic ScienceAsthma Bronchial1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Powder, for solutionRespiratory (inhalation)1600 mg
Powder, for solutionRespiratory (inhalation)480 mg
Powder, for solutionRespiratory (inhalation)100 mg
Powder, for solutionRespiratory (inhalation)100 mg/100mg
Powder, for solutionRespiratory (inhalation)1280 mg
Powder, for solutionRespiratory (inhalation)160 mg
Powder, for solutionRespiratory (inhalation)1600 mg/1600mg
Powder, for solutionRespiratory (inhalation)320 mg
SolutionRespiratory (inhalation)
SolutionRespiratory (inhalation)16 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0678 mg/mLALOGPS
logP-2.7ALOGPS
logP-3.8ChemAxon
logS-3.5ALOGPS
pKa (Strongest Basic)-7ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area26.3 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity55.76 m3·mol-1ChemAxon
Polarizability18.43 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9196
Blood Brain Barrier+0.9595
Caco-2 permeable+0.6374
P-glycoprotein substrateNon-substrate0.7298
P-glycoprotein inhibitor INon-inhibitor0.9567
P-glycoprotein inhibitor IINon-inhibitor0.8384
Renal organic cation transporterNon-inhibitor0.8493
CYP450 2C9 substrateNon-substrate0.8521
CYP450 2D6 substrateNon-substrate0.8612
CYP450 3A4 substrateSubstrate0.5376
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9459
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9407
CYP450 3A4 inhibitorNon-inhibitor0.9475
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9383
Ames testNon AMES toxic0.8427
CarcinogenicityCarcinogens 0.754
BiodegradationReady biodegradable0.9303
Rat acute toxicity2.3602 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.944
hERG inhibition (predictor II)Non-inhibitor0.8091
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as tetraalkylammonium salts. These are organonitrogen compounds containing a quaternary ammonium substituted with four alkyl chains.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Quaternary ammonium salts
Direct Parent
Tetraalkylammonium salts
Alternative Parents
Carboxylic acid esters / Monocarboxylic acids and derivatives / Organopnictogen compounds / Organic salts / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds / Amines / Organic cations
Substituents
Tetraalkylammonium salt / Carboxylic acid ester / Monocarboxylic acid or derivatives / Carboxylic acid derivative / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organic salt / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
quaternary ammonium ion, acetate ester (CHEBI:6804)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. Liu PS, Chen YY, Feng CK, Lin YH, Yu TC: Muscarinic acetylcholine receptors present in human osteoblast and bone tissue. Eur J Pharmacol. 2011 Jan 10;650(1):34-40. doi: 10.1016/j.ejphar.2010.09.031. Epub 2010 Oct 1. [PubMed:20888332]
  2. Fernandez-Rodriguez S, Broadley KJ, Ford WR, Kidd EJ: Increased muscarinic receptor activity of airway smooth muscle isolated from a mouse model of allergic asthma. Pulm Pharmacol Ther. 2010 Aug;23(4):300-7. doi: 10.1016/j.pupt.2010.03.001. Epub 2010 Mar 25. [PubMed:20347047]
  3. Liu T, Xie C, Chen X, Zhao F, Liu AM, Cho DB, Chong J, Yang PC: Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosa. Allergy. 2010 Aug;65(8):969-77. doi: 10.1111/j.1398-9995.2009.02281.x. Epub 2009 Nov 27. [PubMed:19951374]
  4. Gosens R, Rieks D, Meurs H, Ninaber DK, Rabe KF, Nanninga J, Kolahian S, Halayko AJ, Hiemstra PS, Zuyderduyn S: Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells. Eur Respir J. 2009 Dec;34(6):1436-43. doi: 10.1183/09031936.00045209. Epub 2009 May 21. [PubMed:19460789]

Drug created on May 16, 2010 09:28 / Updated on September 21, 2018 20:42