Identification

Name
Methacholine
Accession Number
DB06709
Description

Asthma is a complex condition associated with phenomena such as airway hyperresponsiveness (AHR), in which the smooth muscle in the airways (ASM) excessively contracts in response to stimuli, reducing pulmonary function and causing symptoms such as difficulty breathing.1,2 Although the underlying pathology of AHR is complex, ASM contraction can be stimulated by cholinergic agonists that activate M3 muscarinic receptors that stimulate ASM contraction.2,4,8 Methacholine is a non-specific cholinergic agonist (parasympathomimetic) that acts through muscarinic receptors in the lungs to induce bronchoconstriction.11 In patients with AHR, a lower dose of methacholine is required to induce bronchoconstriction, which forms the basis for the methacholine challenge test to diagnose AHR.10,11

Methacholine was granted FDA approval on October 31, 1986, and is marketed under the trademark PROVOCHOLINE® by Methapharm Inc.11

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 160.234
Monoisotopic: 160.133753825
Chemical Formula
C8H18NO2
Synonyms
  • Acetyl-beta-methylcholine
  • Acetylmethylcholine
  • beta-Methylacetylcholine
  • MCh
  • Methacholine
  • Methacholinum

Pharmacology

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Indication

Methacholine is indicated in adult and pediatric patients aged five years and older without clinically apparent asthma for the diagnosis of bronchial airway hyperactivity via the methacholine challenge test.11

Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
Pharmacodynamics

Methacholine is a non-specific cholinergic agonist (parasympathomimetic) that acts through muscarinic receptors in the lungs to induce bronchoconstriction, which is more significant in patients with asthma than those without. Therefore, methacholine carries a risk of severe bronchoconstriction, especially in patients with pre-existing reduced pulmonary function (typically baseline FEV1 < 60% or < 1.5 L, at least in adults), clinically apparent asthma or wheezing, or other health conditions such as uncontrolled hypertension, aortic aneurysm, or history of myocardial infarction or stroke. Use in patients with epilepsy, vagotonia, peptic ulcer disease, thyroid disease, urinary tract obstruction or other conditions that could be adversely affected by a cholinergic agent is not recommended. Also, there is a potential risk to healthcare workers administering the methacholine challenge test; proper precautions and protective equipment should be used as needed.11

Mechanism of action

Asthma is a complicated condition associated with airway remodelling, including the proliferation of airway smooth muscle (ASM) and altered extracellular matrix, aberrant pro-inflammatory immune responses, and excessive ASM contraction leading to decreased lung function.1,2 Excessive ASM contraction in response to contractile agonists, a phenomenon termed airway hyperresponsiveness (AHR), is a physical manifestation of the altered pulmonary physiology in asthma.2 Although numerous factors, such as increased ASM levels, pro-contractile molecules, pro-inflammatory cytokines, and growth factors, contribute to AHR, one of the key factors in determining ASM tone is regulated by vagal parasympathetic nerve innervation.1,2,3 The response to acetylcholine and other cholinergic agonists at these neuromuscular junctions is predominantly controlled by inhibitory Gi-coupled M2 and excitatory Gq-coupled M3 muscarinic acetylcholine receptors (mAChRs). Activation of M3 receptors results in ASM contraction and resulting bronchoconstriction through downstream calcium-dependent signalling pathways, while M2 activation inhibits neuronal acetylcholine release.2,3,4

Methacholine is a non-specific mAChR agonist, capable of acting on all mAChR subtypes.5,6,7 However, in the context of AHR, methacholine's ability to induce bronchoconstriction through M3 receptors is clinically relevant.2,4,8 In addition, M3 agonism may increase the release of pro-inflammatory cytokines, further contributing to AHR.9 The inhibitory effect of M2 agonism by methacholine is likely also important, as shown by animal studies using mice with impaired M2 function, and by observations that eosinophilic inflammation, such as occurs in asthma, negatively impacts M2 function.3 Hence, asthmatic patients are more sensitive to inhaled cholinergic agonists such as methacholine; this forms the basis for the methacholine challenge test, which diagnoses AHR through an increased methacholine-induced response.10,11

TargetActionsOrganism
AMuscarinic acetylcholine receptor M3
agonist
Humans
AMuscarinic acetylcholine receptor M2
agonist
Humans
UMuscarinic acetylcholine receptor M1
agonist
Humans
UMuscarinic acetylcholine receptor M4
agonist
Humans
UMuscarinic acetylcholine receptor M5
agonist
Humans
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
Adverse Effects
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololAcebutolol 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.
AprotininThe risk or severity of adverse effects can be increased when Aprotinin is combined with Methacholine.
AtenololAtenolol may increase the bronchoconstrictory activities of Methacholine.
BetaineThe risk or severity of adverse effects can be increased when Glycine betaine is combined with Methacholine.
BetaxololBetaxolol may increase the bronchoconstrictory activities of Methacholine.
BisoprololBisoprolol may increase the bronchoconstrictory activities of Methacholine.
CapreomycinThe therapeutic efficacy of Methacholine can be decreased when used in combination with Capreomycin.
CapsaicinThe risk or severity of adverse effects can be increased when Capsaicin is combined with Methacholine.
Interactions
Improve patient outcomes
Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.
Learn more
Food Interactions
  • Take with or without food.

Products

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
Product Ingredients
IngredientUNIICASInChI Key
Methacholine chloride0W5ETF9M2K62-51-1JHPHVAVFUYTVCL-UHFFFAOYSA-M
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Methacholine Chloride, USPPowder, for solutionRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada flag
Methacholine Chloride, USPPowder, for solutionRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada flag
Methacholine Chloride, USPPowder, for solutionRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada flag
Methacholine Chloride, USPPowder, for solutionRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada flag
Methacholine Chloride, USPPowder, for solutionRespiratory (inhalation)Panda Pharmaceuticals Inc.Not applicableNot applicableCanada flag
Methacholine OmegaPowder, for solutionRespiratory (inhalation)Omega Laboratories Ltd2006-03-27Not applicableCanada flag
Methacholine OmegaPowder, for solutionRespiratory (inhalation)Omega Laboratories Ltd2006-03-21Not applicableCanada flag
Methacholine OmegaPowder, for solutionRespiratory (inhalation)Omega Laboratories Ltd2006-07-03Not applicableCanada flag
ProvocholinePowder, for solution100 mg/100mgRespiratory (inhalation)Methapharm Inc.2013-03-27Not applicableUS flag
ProvocholinePowder, for solution1600 mgRespiratory (inhalation)Methapharm, Inc.2008-02-28Not applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
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 flag
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 flag
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 flag
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 flag
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 flag
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 flag
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 flag
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 flag
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 flag
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 flag

Categories

ATC Codes
V04CX03 — Methacholine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Aliphatic acyclic compound / Amine / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Organic cation / Organic oxide / Organic oxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
quaternary ammonium ion, acetate ester (CHEBI:6804)

Chemical Identifiers

UNII
03V657ZD3V
CAS number
55-92-5
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

References

General References
  1. Aghasafari P, George U, Pidaparti R: A review of inflammatory mechanism in airway diseases. Inflamm Res. 2019 Jan;68(1):59-74. doi: 10.1007/s00011-018-1191-2. Epub 2018 Oct 10. [PubMed:30306206]
  2. Lam M, Lamanna E, Bourke JE: Regulation of Airway Smooth Muscle Contraction in Health and Disease. Adv Exp Med Biol. 2019;1124:381-422. doi: 10.1007/978-981-13-5895-1_16. [PubMed:31183836]
  3. Castro JM, Resende RR, Mirotti L, Florsheim E, Albuquerque LL, Lino-dos-Santos-Franco A, Gomes E, de Lima WT, de Franco M, Ribeiro OG, Russo M: Role of m2 muscarinic receptor in the airway response to methacholine of mice selected for minimal or maximal acute inflammatory response. Biomed Res Int. 2013;2013:805627. doi: 10.1155/2013/805627. Epub 2013 Apr 18. [PubMed:23691511]
  4. Gosens R, Bromhaar MM, Tonkes A, Schaafsma D, Zaagsma J, Nelemans SA, Meurs H: Muscarinic M(3) receptor-dependent regulation of airway smooth muscle contractile phenotype. Br J Pharmacol. 2004 Mar;141(6):943-50. doi: 10.1038/sj.bjp.0705709. Epub 2004 Mar 1. [PubMed:14993104]
  5. Gonzalez JC, Albinana E, Baldelli P, Garcia AG, Hernandez-Guijo JM: Presynaptic muscarinic receptor subtypes involved in the enhancement of spontaneous GABAergic postsynaptic currents in hippocampal neurons. Eur J Neurosci. 2011 Jan;33(1):69-81. doi: 10.1111/j.1460-9568.2010.07475.x. Epub 2010 Nov 23. [PubMed:21091801]
  6. Meyer EM, Otero DH: Pharmacological and ionic characterizations of the muscarinic receptors modulating [3H]acetylcholine release from rat cortical synaptosomes. J Neurosci. 1985 May;5(5):1202-7. [PubMed:3998816]
  7. Tulic MK, Wale JL, Petak F, Sly PD: Muscarinic blockade of methacholine induced airway and parenchymal lung responses in anaesthetised rats. Thorax. 1999 Jun;54(6):531-7. doi: 10.1136/thx.54.6.531. [PubMed:10335008]
  8. Borchers MT, Biechele T, Justice JP, Ansay T, Cormier S, Mancino V, Wilkie TM, Simon MI, Lee NA, Lee JJ: Methacholine-induced airway hyperresponsiveness is dependent on Galphaq signaling. Am J Physiol Lung Cell Mol Physiol. 2003 Jul;285(1):L114-20. doi: 10.1152/ajplung.00322.2002. Epub 2003 Feb 28. [PubMed:12611815]
  9. 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]
  10. Davis BE, Blais CM, Cockcroft DW: Methacholine challenge testing: comparative pharmacology. J Asthma Allergy. 2018 May 14;11:89-99. doi: 10.2147/JAA.S160607. eCollection 2018. [PubMed:29785128]
  11. FDA Approved Drug Products: PROVOCHOLINE (methacholine chloride) inhalation [Link]
Human Metabolome Database
HMDB0015654
KEGG Compound
C07471
PubChem Compound
1993
PubChem Substance
99443261
ChemSpider
1916
BindingDB
48918
RxNav
155080
ChEBI
6804
ChEMBL
CHEMBL978
PharmGKB
PA165958382
Wikipedia
Methacholine
AHFS Codes
  • 36:89.00* — Other Diagnostics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableAsthma1
4CompletedDiagnosticAsthma1
4Not Yet RecruitingBasic ScienceAsthma / Cough Variant Asthma / Coughing1
4Unknown StatusNot AvailableAsthma1
3CompletedDiagnosticAsthma2
3CompletedOtherAsthma1
3CompletedPreventionAsthma1
1CompletedTreatmentAsthma / Diabetes Mellitus1
1CompletedTreatmentHealthy Volunteers1
Not AvailableActive Not RecruitingBasic ScienceAsthma / Cough Variant Asthma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Powder, for solutionRespiratory (inhalation)0.2 %
Powder, for solutionRespiratory (inhalation)1 %
Powder, for solutionRespiratory (inhalation)6.4 %
Powder, for solutionRespiratory (inhalation)
Powder, for solutionRespiratory (inhalation)100 mg/100mg
Powder, for solutionRespiratory (inhalation)100 mg
Powder, for solutionRespiratory (inhalation)1280 mg
Powder, for solutionRespiratory (inhalation)160 mg
Powder, for solutionRespiratory (inhalation)1600 mg
Powder, for solutionRespiratory (inhalation)1600 mg/1600mg
Powder, for solutionRespiratory (inhalation)320 mg
SolutionRespiratory (inhalation)
SolutionRespiratory (inhalation)
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)170-174https://www.tcichemicals.com/GB/en/p/M0073
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

Targets

Kind
Protein
Organism
Humans
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]
  5. Gosens R, Bromhaar MM, Tonkes A, Schaafsma D, Zaagsma J, Nelemans SA, Meurs H: Muscarinic M(3) receptor-dependent regulation of airway smooth muscle contractile phenotype. Br J Pharmacol. 2004 Mar;141(6):943-50. doi: 10.1038/sj.bjp.0705709. Epub 2004 Mar 1. [PubMed:14993104]
  6. Borchers MT, Biechele T, Justice JP, Ansay T, Cormier S, Mancino V, Wilkie TM, Simon MI, Lee NA, Lee JJ: Methacholine-induced airway hyperresponsiveness is dependent on Galphaq signaling. Am J Physiol Lung Cell Mol Physiol. 2003 Jul;285(1):L114-20. doi: 10.1152/ajplung.00322.2002. Epub 2003 Feb 28. [PubMed:12611815]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
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. Castro JM, Resende RR, Mirotti L, Florsheim E, Albuquerque LL, Lino-dos-Santos-Franco A, Gomes E, de Lima WT, de Franco M, Ribeiro OG, Russo M: Role of m2 muscarinic receptor in the airway response to methacholine of mice selected for minimal or maximal acute inflammatory response. Biomed Res Int. 2013;2013:805627. doi: 10.1155/2013/805627. Epub 2013 Apr 18. [PubMed:23691511]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
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. Tulic MK, Wale JL, Petak F, Sly PD: Muscarinic blockade of methacholine induced airway and parenchymal lung responses in anaesthetised rats. Thorax. 1999 Jun;54(6):531-7. doi: 10.1136/thx.54.6.531. [PubMed:10335008]
  2. Meyer EM, Otero DH: Pharmacological and ionic characterizations of the muscarinic receptors modulating [3H]acetylcholine release from rat cortical synaptosomes. J Neurosci. 1985 May;5(5):1202-7. [PubMed:3998816]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Guanyl-nucleotide exchange factor 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
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 Da
References
  1. Gonzalez JC, Albinana E, Baldelli P, Garcia AG, Hernandez-Guijo JM: Presynaptic muscarinic receptor subtypes involved in the enhancement of spontaneous GABAergic postsynaptic currents in hippocampal neurons. Eur J Neurosci. 2011 Jan;33(1):69-81. doi: 10.1111/j.1460-9568.2010.07475.x. Epub 2010 Nov 23. [PubMed:21091801]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
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
CHRM5
Uniprot ID
P08912
Uniprot Name
Muscarinic acetylcholine receptor M5
Molecular Weight
60073.205 Da
References
  1. Gonzalez JC, Albinana E, Baldelli P, Garcia AG, Hernandez-Guijo JM: Presynaptic muscarinic receptor subtypes involved in the enhancement of spontaneous GABAergic postsynaptic currents in hippocampal neurons. Eur J Neurosci. 2011 Jan;33(1):69-81. doi: 10.1111/j.1460-9568.2010.07475.x. Epub 2010 Nov 23. [PubMed:21091801]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
This action is predicted based on inhibition studies of inhaled β-agonists and requires confirmation by studies explicitly demonstrating inhibition of OCTN2 by methacholine.
General Function
Symporter activity
Specific Function
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 cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Gnadt M, Trammer B, Freiwald M, Kardziev B, Bayliss MK, Edwards CD, Schmidt M, Friedel G, Hogger P: Methacholine delays pulmonary absorption of inhaled beta(2)-agonists due to competition for organic cation/carnitine transporters. Pulm Pharmacol Ther. 2012 Feb;25(1):124-34. doi: 10.1016/j.pupt.2011.12.009. Epub 2012 Jan 5. [PubMed:22245488]

Drug created on May 16, 2010 15:28 / Updated on February 24, 2021 23:07