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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

Molecular Formula C8H18NO2
Molecular Weight 160.234
Charge 1
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry MIXED
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description

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.

CNS Activity

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
59.0 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Diagnostic
PROVOCHOLINE

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Sample Use Guides

In Vivo Use Guide
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.
Substance Class Chemical
Record UNII
03V657ZD3V
Record Status Validated (UNII)
Record Version