Identification

Name
Methacholine
Accession Number
DB06709
Type
Small Molecule
Groups
Approved
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 solution320 mgRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada
Methacholine Chloride, USPPowder, for solution1600 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 solution1600 mgRespiratory (inhalation)Omega Laboratories Ltd2006-07-03Not applicableCanada
Methacholine OmegaPowder, for solution100 mgRespiratory (inhalation)Omega Laboratories Ltd2006-03-27Not applicableCanada
Methacholine OmegaPowder, for solution480 mgRespiratory (inhalation)Omega Laboratories Ltd2006-03-21Not applicableCanada
ProvocholinePowder, for solution100 mgRespiratory (inhalation)Methapharm, Inc.1999-04-01Not applicableCanada
ProvocholinePowder, for solution1600 mg/1600mgRespiratory (inhalation)Methapharm, Inc.2016-08-292017-10-07Us
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.

Structured Indications
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
DrugInteractionDrug group
1,10-PhenanthrolineThe risk or severity of adverse effects can be increased when 1,10-Phenanthroline is combined with Methacholine.Experimental
AcebutololAcebutolol may increase the bronchoconstrictory activities of Methacholine.Approved
AlprenololAlprenolol may increase the bronchoconstrictory activities of Methacholine.Approved, Withdrawn
AmbenoniumThe risk or severity of adverse effects can be increased when Ambenonium is combined with Methacholine.Approved
ArotinololArotinolol may increase the bronchoconstrictory activities of Methacholine.Approved, Investigational
AtenololAtenolol may increase the bronchoconstrictory activities of Methacholine.Approved
BefunololBefunolol may increase the bronchoconstrictory activities of Methacholine.Experimental
BetaxololBetaxolol may increase the bronchoconstrictory activities of Methacholine.Approved
BevantololBevantolol may increase the bronchoconstrictory activities of Methacholine.Approved
BisoprololBisoprolol may increase the bronchoconstrictory activities of Methacholine.Approved
BopindololBopindolol may increase the bronchoconstrictory activities of Methacholine.Approved
BucindololBucindolol may increase the bronchoconstrictory activities of Methacholine.Investigational
BufuralolBufuralol may increase the bronchoconstrictory activities of Methacholine.Experimental, Investigational
BupranololBupranolol may increase the bronchoconstrictory activities of Methacholine.Approved
CarteololCarteolol may increase the bronchoconstrictory activities of Methacholine.Approved
CarvedilolCarvedilol may increase the bronchoconstrictory activities of Methacholine.Approved, Investigational
CeliprololCeliprolol may increase the bronchoconstrictory activities of Methacholine.Approved, Investigational
CimetropiumMethacholine may decrease the anticholinergic activities of Cimetropium.Experimental, Investigational
CloranololCloranolol may increase the bronchoconstrictory activities of Methacholine.Experimental
CoumaphosThe risk or severity of adverse effects can be increased when Coumaphos is combined with Methacholine.Vet Approved
DecamethoniumThe risk or severity of adverse effects can be increased when Decamethonium is combined with Methacholine.Approved
DemecariumThe risk or severity of adverse effects can be increased when Demecarium is combined with Methacholine.Approved
DichlorvosThe risk or severity of adverse effects can be increased when Dichlorvos is combined with Methacholine.Vet Approved
DistigmineThe risk or severity of adverse effects can be increased when Distigmine is combined with Methacholine.Experimental
DonepezilThe risk or severity of adverse effects can be increased when Donepezil is combined with Methacholine.Approved
EchothiophateThe risk or severity of adverse effects can be increased when Echothiophate is combined with Methacholine.Approved
EdrophoniumThe risk or severity of adverse effects can be increased when Edrophonium is combined with Methacholine.Approved
EpanololEpanolol may increase the bronchoconstrictory activities of Methacholine.Experimental
EsmololEsmolol may increase the bronchoconstrictory activities of Methacholine.Approved
FenthionThe risk or severity of adverse effects can be increased when Fenthion is combined with Methacholine.Vet Approved
GalantamineThe risk or severity of adverse effects can be increased when Galantamine is combined with Methacholine.Approved
Gallamine TriethiodideThe risk or severity of adverse effects can be increased when Gallamine Triethiodide is combined with Methacholine.Approved
Ginkgo bilobaThe risk or severity of adverse effects can be increased when Ginkgo biloba is combined with Methacholine.Approved, Investigational, Nutraceutical
Huperzine AThe risk or severity of adverse effects can be increased when Huperzine A is combined with Methacholine.Investigational
IndenololIndenolol may increase the bronchoconstrictory activities of Methacholine.Withdrawn
IpidacrineThe risk or severity of adverse effects can be increased when Ipidacrine is combined with Methacholine.Experimental
IsoflurophateThe risk or severity of adverse effects can be increased when Isoflurophate is combined with Methacholine.Approved, Investigational, Withdrawn
LabetalolLabetalol may increase the bronchoconstrictory activities of Methacholine.Approved
LandiololLandiolol may increase the bronchoconstrictory activities of Methacholine.Investigational
LevobunololLevobunolol may increase the bronchoconstrictory activities of Methacholine.Approved
MalathionThe risk or severity of adverse effects can be increased when Malathion is combined with Methacholine.Approved, Investigational
MefloquineThe risk or severity of adverse effects can be increased when Mefloquine is combined with Methacholine.Approved
MemantineThe risk or severity of adverse effects can be increased when Memantine is combined with Methacholine.Approved, Investigational
MepindololMepindolol may increase the bronchoconstrictory activities of Methacholine.Experimental
Methanesulfonyl FluorideThe risk or severity of adverse effects can be increased when Methanesulfonyl Fluoride is combined with Methacholine.Investigational
MetipranololMetipranolol may increase the bronchoconstrictory activities of Methacholine.Approved
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Methacholine.Approved, Investigational
MetoprololMetoprolol may increase the bronchoconstrictory activities of Methacholine.Approved, Investigational
MinaprineThe risk or severity of adverse effects can be increased when Minaprine is combined with Methacholine.Approved
NadololNadolol may increase the bronchoconstrictory activities of Methacholine.Approved
NebivololNebivolol may increase the bronchoconstrictory activities of Methacholine.Approved, Investigational
NeostigmineThe risk or severity of adverse effects can be increased when Neostigmine is combined with Methacholine.Approved, Vet Approved
OxprenololOxprenolol may increase the bronchoconstrictory activities of Methacholine.Approved
ParaoxonThe risk or severity of adverse effects can be increased when Paraoxon is combined with Methacholine.Experimental
PenbutololPenbutolol may increase the bronchoconstrictory activities of Methacholine.Approved, Investigational
PhysostigmineThe risk or severity of adverse effects can be increased when Physostigmine is combined with Methacholine.Approved
PindololPindolol may increase the bronchoconstrictory activities of Methacholine.Approved
Platelet Activating FactorPlatelet Activating Factor may increase the bronchoconstrictory activities of Methacholine.Experimental
PractololPractolol may increase the bronchoconstrictory activities of Methacholine.Approved
PropranololPropranolol may increase the bronchoconstrictory activities of Methacholine.Approved, Investigational
PyridostigmineThe risk or severity of adverse effects can be increased when Pyridostigmine is combined with Methacholine.Approved
RivastigmineThe risk or severity of adverse effects can be increased when Rivastigmine is combined with Methacholine.Approved, Investigational
SotalolSotalol may increase the bronchoconstrictory activities of Methacholine.Approved
TacrineThe risk or severity of adverse effects can be increased when Tacrine is combined with Methacholine.Investigational, Withdrawn
TalinololTalinolol may increase the bronchoconstrictory activities of Methacholine.Investigational
TertatololTertatolol may increase the bronchoconstrictory activities of Methacholine.Experimental
TimololTimolol may increase the bronchoconstrictory activities of Methacholine.Approved
TrichlorfonThe risk or severity of adverse effects can be increased when Trichlorfon is combined with Methacholine.Vet Approved
TubocurarineThe risk or severity of adverse effects can be increased when Tubocurarine is combined with Methacholine.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15654
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
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 January 14, 2018 10:04