Pharmacology · Muscarinic (cholinergic) agonists
Methacholine !
An inhaled muscarinic agonist used only as a diagnostic test: people with asthma narrow their airways at much lower doses.
Updated 2026-11-01
No structure of methacholine bound to its receptor exists. The figure shows iperoxo, a potent research agonist, in the acetylcholine (orthosteric) pocket of the active human M3 muscarinic receptor, the subtype on glands, the eye and the bladder that methacholine stimulates.
Mechanism of action
Methacholine is acetylcholine with an extra methyl group: it resists cholinesterase better and acts mainly on muscarinic receptors. Inhaled, it contracts airway smooth muscle. Everyone narrows the airways a little, but people with hyperresponsive airways, as in asthma, react strongly at low concentrations, which the bronchial challenge test measures with spirometry.
- Inhaled in increasing concentrations
- Activates M3 receptors of airway smooth muscle
- Airways narrow; spirometry falls
- A strong response at low doses means hyperresponsive airways
Pharmacokinetics
- Absorption
- Inhaled from a nebulizer; acts locally in the airways
- Metabolism
- Hydrolysed by acetylcholinesterase more slowly than acetylcholine
Indications
- Bronchial challenge test for airway hyperresponsiveness when asthma is suspected but not clinically clear Asthma →
Adverse effects
Common
- Cough, chest tightness and wheeze
- Shortness of breath
- Dizziness and discomfort
Contraindications
- Severe airflow limitation
- Recent heart attack or stroke
- Uncontrolled high blood pressure
- Pregnancy
Key interactions
- Beta blockers
- Exaggerated or prolonged airway response
- Inhaled antimuscarinics (ipratropium, tiotropium)
- Blunt the response and can make the test falsely negative
What is monitored
- Spirometry after each concentration
- Symptoms, oxygen saturation and breath sounds during and after the test
Administration and safety
- Performed only in a pulmonary function laboratory, with oxygen, resuscitation equipment and an inhaled bronchodilator ready
- A bronchodilator is given at the end if the airways have narrowed
Nursing care
- Confirm that pregnancy and recent heart attack or stroke have been ruled out
- Ask which inhalers and beta blockers the person uses
- Stay with the patient and watch for wheeze or distress
Pregnancy and breastfeeding
Pregnancy is a contraindication to methacholine testing.
Test yourself
Think of the answer, then tap the question to see it.
What is methacholine used for?
Only for the bronchial challenge test that detects airway hyperresponsiveness, as in asthma.
Which medicine must be ready during the test?
An inhaled bronchodilator (beta-2 agonist), with oxygen and resuscitation equipment.
How does methacholine differ chemically from acetylcholine?
It has an extra β-methyl group, which makes it more resistant to cholinesterase and more muscarinic.
Related drugs
Related conditions
← Back to the class: Muscarinic (cholinergic) agonists
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 11 (McGraw Hill, 2023); Methacholine Challenge Test (American Lung Association, 2024); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.