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Details

Stereochemistry RACEMIC
Molecular Formula C8H18NO2
Molecular Weight 160.234
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(C)=O

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
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
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
Effects of smooth muscle activation on axial mechanical properties of excised canine bronchi.
2001 Apr
Changes in airway resistance by simultaneous exposure to TNF-alpha and IL-1beta in perfused rat lungs.
2001 Apr
Respiratory effects of a single dive to 50 meters in sport divers with asymptomatic respiratory atopy.
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
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
Protein kinase C and G(i/o) proteins are involved in adenosine- and ischemic preconditioning-mediated renal protection.
2001 Feb
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
Inhaled mannitol shifts exhaled nitric oxide in opposite directions in asthmatics and healthy subjects.
2001 Jan
Pulmonary function response to EDTA, an additive in nebulized bronchodilators.
2001 Jan
Secretion and gene expression of secretory leukocyte protease inhibitor by human airway submucosal glands.
2001 Jan
Enhancement of goblet cell hyperplasia and airway hyperresponsiveness by salbutamol in a rat model of atopic asthma.
2001 Jan
Incidence and host determinants of probable occupational asthma in apprentices exposed to laboratory animals.
2001 Mar
Measurements of resistance by the interrupter technique and of transcutaneous partial pressure of oxygen in young children during methacholine challenge.
2001 Mar
Assessment of oxidant stress in allergic asthma by measurement of the major urinary metabolite of F2-isoprostane, 15-F2t-IsoP (8-iso-PGF2alpha).
2001 Mar
Drug treatment of airway inflammation in asthma.
2001 Mar
Inhibition of eosinophilic inflammation in allergen-challenged TNF receptor p55/p75--and TNF receptor p55-deficient mice.
2001 Mar
Role of K+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle.
2001 Mar 9
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
Occupational asthma caused by exposure to cyanoacrylate.
2001 May
Validation of a new questionnaire on asthma, allergic rhinitis, and conjunctivitis in young adults.
2001 May
Normally suppressing CD40 coregulatory signals delivered by airway macrophages to TH2 lymphocytes are defective in patients with atopic asthma.
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 [WHO-DD]
Common Name English
METHACHOLINE CATION
Common Name English
METHACHOLINE [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175369
Created by admin on Fri Dec 15 15:54:32 UTC 2023 , Edited by admin on Fri Dec 15 15:54:32 UTC 2023
NCI_THESAURUS C1937
Created by admin on Fri Dec 15 15:54:32 UTC 2023 , Edited by admin on Fri Dec 15 15:54:32 UTC 2023
NDF-RT N0000175884
Created by admin on Fri Dec 15 15:54:32 UTC 2023 , Edited by admin on Fri Dec 15 15:54:32 UTC 2023
Code System Code Type Description
IUPHAR
7438
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PRIMARY
DAILYMED
03V657ZD3V
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PRIMARY
WIKIPEDIA
METHACHOLINE
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PRIMARY
RXCUI
155080
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PRIMARY RxNorm
EPA CompTox
DTXSID2046967
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PRIMARY
CAS
55-92-5
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PRIMARY
DRUG BANK
DB06709
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PRIMARY
SMS_ID
100000085927
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PRIMARY
NCI_THESAURUS
C61837
Created by admin on Fri Dec 15 15:54:32 UTC 2023 , Edited by admin on Fri Dec 15 15:54:32 UTC 2023
PRIMARY
FDA UNII
03V657ZD3V
Created by admin on Fri Dec 15 15:54:32 UTC 2023 , Edited by admin on Fri Dec 15 15:54:32 UTC 2023
PRIMARY
CHEBI
6804
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PRIMARY
EVMPD
SUB03201MIG
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PRIMARY
DRUG CENTRAL
1726
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PRIMARY
PUBCHEM
1993
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PRIMARY