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Details

Stereochemistry RACEMIC
Molecular Formula C8H18NO2
Molecular Weight 160.2343
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 1

SHOW SMILES / InChI
Structure of METHACHOLINE

SMILES

CC(C[N+](C)(C)C)OC(=O)C

InChI

InChIKey=NZWOPGCLSHLLPA-UHFFFAOYSA-N
InChI=1S/C8H18NO2/c1-7(11-8(2)10)6-9(3,4)5/h7H,6H2,1-5H3/q+1

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019193s013lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/9622546

Methacholine (trade name Provocholine) is a synthetic choline ester that acts as a muscarinic receptor agonist. Methacholine is primarily used to diagnose bronchial hyperreactivity, which is the hallmark of asthma and also occurs in chronic obstructive pulmonary disease. This is accomplished through the bronchial challenge test, or methacholine challenge, in which a subject inhales aerosolized methacholine, leading to bronchoconstriction.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Diagnostic
PROVOCHOLINE

Approved Use

Provocholine® (methacholine chloride powder for inhalation) is indicated for the diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma.

Launch Date

5.31100795E11
Doses

Doses

DosePopulationAdverse events​
16 mg/mL 5 times / day multiple, respiratory (max)
Recommended
Dose: 16 mg/mL, 5 times / day
Route: respiratory
Route: multiple
Dose: 16 mg/mL, 5 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Bronchial airway hyperreactivity
Sources: Page: p.1
Disc. AE: Bronchoconstriction...
AEs leading to
discontinuation/dose reduction:
Bronchoconstriction (severe)
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Bronchoconstriction severe
Disc. AE
16 mg/mL 5 times / day multiple, respiratory (max)
Recommended
Dose: 16 mg/mL, 5 times / day
Route: respiratory
Route: multiple
Dose: 16 mg/mL, 5 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Bronchial airway hyperreactivity
Sources: Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Noninvasive method to measure airway obstruction in nonanesthetized allergen-sensitized and challenged mice.
2001
Bronchoconstrictor reactivity to NKA in allergic dogs: a comparison to histamine and methacholine.
2001
The effect of acute alteration in oxygen tension on the bronchodilator response to salbutamol in vitro and in vivo in man.
2001
Effect of the cyclooxygenase-2 inhibitor celecoxib on bronchial responsiveness and cough reflex sensitivity in asthmatics.
2001
Airway foreign body with clinical features mimicking bronchial asthma.
2001
Bronchial hyperresponsiveness and exhaled nitric oxide in patients with cardiac disease.
2001
Changes in indices of airway hyperresponsiveness during one year of treatment with inhaled corticosteroids in patients with asthma.
2001 Apr
Increased frequency of Chlamydia pneumoniae antibodies in patients with asthma.
2001 Apr
Glucocorticoid treatment increases inhibitory m(2) muscarinic receptor expression and function in the airways.
2001 Apr
Conditioned medium from hypoxic cytotrophoblasts alters arterial function.
2001 Apr
Three years of specific immunotherapy with house-dust-mite extracts in patients with rhinitis and asthma: significant improvement of allergen-specific parameters and of nonspecific bronchial hyperreactivity.
2001 Apr
Tumour necrosis factor-alpha: the role of this multifunctional cytokine in asthma.
2001 Apr
Gibbs sampling-based segregation analysis of asthma-associated quantitative traits in a population-based sample of nuclear families.
2001 Apr
Changes in airway resistance by simultaneous exposure to TNF-alpha and IL-1beta in perfused rat lungs.
2001 Apr
Hexachlorobenzene-induced eosinophilic and granulomatous lung inflammation is associated with in vivo airways hyperresponsiveness in the Brown Norway rat.
2001 Apr 1
Enhanced airway Th2 response after allergen challenge in mice deficient in CC chemokine receptor-2 (CCR2).
2001 Apr 15
Respiratory effects of a single dive to 50 meters in sport divers with asymptomatic respiratory atopy.
2001 Feb
G(q/11) and G(i/o) activation profiles in CHO cells expressing human muscarinic acetylcholine receptors: dependence on agonist as well as receptor-subtype.
2001 Feb
The lack of the bronchoprotective and not the bronchodilatory ability of deep inspiration is associated with airway hyperresponsiveness.
2001 Feb
Protective effects of volatile agents against methacholine-induced bronchoconstriction in rats.
2001 Feb
Blockade of eosinophil migration and airway hyperresponsiveness by cPLA2-inhibition.
2001 Feb
Coronary and laryngeal spasm provoked by methacholine inhalation.
2001 Feb
Regular inhaled salbutamol : effect on airway responsiveness to methacholine and adenosine 5'-monophosphate and tolerance to bronchoprotection.
2001 Feb
Oilseed rape flour: another allergen causing occupational asthma among farmers.
2001 Feb
ATS guidelines for methacholine and exercise challenge testing.
2001 Jan
Acute anti-inflammatory effects of inhaled budesonide in asthma: a randomized controlled trial.
2001 Jan
Abnormal responses to endothelial agonists in Raynaud's phenomenon and scleroderma.
2001 Jan
Linkage between bronchial responsiveness to methacholine and gene markers of IL-4 cytokine gene cluster and T-cell receptor alpha/delta gene complex in Korean nuclear families.
2001 Jan
[Asthma related to inhalation of Plantago ovata].
2001 Jan 13
Seasonal variability of non-specific bronchial responsiveness in asthmatic patients with allergy to house dust mites.
2001 Jan-Feb
Airways hyperresponsiveness and the effects of lung inflation.
2001 Jan-Mar
Correlation between airway hyperresponsiveness and airway inflammation in a young adult population: eosinophil, ECP, and cytokine levels in induced sputum.
2001 Mar
Airway responses to a diluent used in the methacholine challenge test.
2001 Mar
High-resolution computed tomographic evaluation of airway distensibility and the effects of lung inflation on airway caliber in healthy subjects and individuals with asthma.
2001 Mar
Measurements of resistance by the interrupter technique and of transcutaneous partial pressure of oxygen in young children during methacholine challenge.
2001 Mar
Effect of salmeterol on allergen-induced airway inflammation in mild allergic asthma.
2001 Mar
The transcription factor early growth-response factor 1 modulates tumor necrosis factor-alpha, immunoglobulin E, and airway responsiveness in mice.
2001 Mar
Temporal association between airway hyperresponsiveness and airway eosinophilia in ovalbumin-sensitized mice.
2001 Mar
Drug treatment of airway inflammation in asthma.
2001 Mar
Airway administration of Escherichia coli endotoxin to mice induces glucocorticosteroid-resistant bronchoconstriction and vasopermeation.
2001 Mar
Inhibition of eosinophilic inflammation in allergen-challenged TNF receptor p55/p75--and TNF receptor p55-deficient mice.
2001 Mar
Methacholine challenge testing in Reserve Officer Training Corps cadets.
2001 Mar
Relationship between bronchial hyperresponsiveness and development of asthma in wheezy infants.
2001 Mar
Enhanced production of leukotrienes by peripheral leukocytes and specific IgE antibodies in patients with chronic obstructive pulmonary disease.
2001 Mar
A comparison of ovariectomy models for estrogen studies.
2001 Mar
Muscarinic depression of synaptic transmission in the epileptogenic GABA withdrawal syndrome focus.
2001 May
Airway inflammation and bronchial hyperresponsiveness after Mycoplasma pneumoniae infection in a murine model.
2001 May
Eosinophil markers in blood, serum, and urine for monitoring the clinical course in childhood asthma: impact of budesonide treatment and withdrawal.
2001 May
Mutation screening of the muscarinic M(2) and M(3) receptor genes in normal and asthmatic subjects.
2001 May
Endothelial function during stimulation of renin-angiotensin system by low-sodium diet in humans.
2001 May
Patents

Sample Use Guides

Provocholine is inhaled using a standardized procedure. The challenge is performed by giving a subject ascending serial concentrations of Provocholine. At each concentration, five breaths are administered by a nebulizer that permits intermittent delivery time of 0.6 seconds by a breath-actuated timing device (dosimeter). At each of five inhalations of a serial concentration, the subject begins at functional residual capacity (FRC) and slowly and completely inhales the dose delivered. Within 5 minutes, FEV1 values are determined. The procedure ends either when there is a 20% or greater reduction in the FEV1 compared with the baseline sodium chloride solution value (i.e., a positive response) or if 188.88 total cumulative units have been administered and the FEV1 has been reduced by 14 % or less (i.e., a negative response). If there is a reduction of 15% to 19% in the FEV, compared with baseline, either the challenge may be repeated at that concentration or a higher concentration may be given as long as the dosage administered does not result in total cumulative units exceeding 188.88.
Route of Administration: Respiratory
In Vitro Use Guide
Agonist activity of methacholine was determined using assay of accumulation of [3H]inositol monophosphate. The CHO cells were labeled in 12-well plates with 1 uCi/mL myo-[3H]inositol for 24 h. Wells contained ca. 3* 10^5 cells in a volume of 1 mL. Cells were then washed once with Hank’s balanced salt media containing 20 mM HEPES buffer (pH 7.4) and were then incubated in the buffered Hank’s media containing 10 mM LiCl at room temperature for 15 min. Muscarinic agents were then added to each well. After incubation for 1 h at 37 °C, the medium was aspirated and replaced with 750 uL of cold 20 mM aqueous formic acid. After 35 min at 4 °C, the formic acid was removed and replaced with 250 uL of 60 mM NH4OH. The inositol monophosphate in the NH4OH solution was isolated by anionexchange chromatography19 and counted for tritium in Hydrofluor scintillation fluid. Cells were treated with 0.001 - 10 uM of methacholine, EC50 was determined to be 120 nM.
Name Type Language
METHACHOLINE
VANDF   WHO-DD  
Common Name English
1-PROPANAMINIUM, 2-(ACETYLOXY)-N,N,N-TRIMETHYL-, (+/-)-
Systematic Name English
METHACHOLINE ION
Common Name English
METHACHOLINE CATION
Common Name English
METHACHOLINE [WHO-DD]
Common Name English
METHACHOLINE [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175369
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
NCI_THESAURUS C1937
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
NDF-RT N0000175884
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
Code System Code Type Description
IUPHAR
7438
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY
WIKIPEDIA
METHACHOLINE
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY
RXCUI
155080
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY RxNorm
EPA CompTox
55-92-5
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY
CAS
55-92-5
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY
DRUG BANK
DB06709
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY
NCI_THESAURUS
C61837
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY
FDA UNII
03V657ZD3V
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY
EVMPD
SUB03201MIG
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY
DRUG CENTRAL
1726
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY
PUBCHEM
1993
Created by admin on Sat Jun 26 06:56:45 UTC 2021 , Edited by admin on Sat Jun 26 06:56:45 UTC 2021
PRIMARY