Methacholine

Methacholine (INN, USAN) (trade name Provocholine), also known as acetyl-β-methylcholine, is a synthetic choline ester that acts as a non-selective muscarinic receptor agonist in the parasympathetic nervous system.

Methacholine

Clinical data
Trade names	Provocholine
AHFS/Drugs.com	Consumer Drug Information
License data	US DailyMed: Methacholine
Routes of administration	Respiratory
ATC code	V04CX03 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: ℞-only
Identifiers
IUPAC name 2-(Acetyloxy)-N,N,N-trimethylpropan-1-aminium
CAS Number	55-92-5 N 62-51-1 (chloride)
PubChem CID	6114
DrugBank	DB06709 Y
ChemSpider	5888 Y
UNII	03V657ZD3V
KEGG	D04970 Y
ChEBI	CHEBI:50142 Y
ChEMBL	ChEMBL978 N
CompTox Dashboard (EPA)	DTXSID2046967
Chemical and physical data
Formula	C8H18NO2+
Molar mass	160.237 g·mol−1
3D model (JSmol)	Interactive image
SMILES [Cl-].O=C(OC(C)C[N+](C)(C)C)C
InChI InChI=1S/C8H18NO2.ClH/c1-7(11-8(2)10)6-9(3,4)5;/h7H,6H2,1-5H3;1H/q+1;/p-1 Y Key:JHPHVAVFUYTVCL-UHFFFAOYSA-M Y
NY (what is this?)  (verify)

Medical uses

Methacholine is primarily used to diagnose bronchial hyperreactivity,^[1] 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. Other therapeutic uses are limited by its adverse cardiovascular effects, such as bradycardia and hypotension, which arise from its function as a cholinomimetic.

Pharmacology

It is highly active at all of the muscarinic receptors, but has little effect on the nicotinic receptors. Methacholine has a charged quaternary amine structure, rendering it insoluble in lipid cell membranes. Clinically, this means that it will not cross the blood–brain barrier and has poor absorption from the gastrointestinal tract. It is broken down at a relatively slow rate within the body, due to its relative resistance to acetylcholinesterases.

The chemical structure of methacholine is derived from acetylcholine by the substitution of a methyl group on the β carbon; this methyl group increases selectivity for muscarinic receptors over nicotinic receptors. The quaternary ammonium group is essential for activity.

Contraindications

Use of methacholine is contraindicated in patients with recent heart attack or stroke, uncontrolled hypertension, known severe airway disease, or aortic aneurysm. It may be used with caution by nursing or pregnant mothers and patients taking certain medications for myasthenia gravis.^[2]