Methacholine: Formula, Presentation, Indications, Mechanism of Action, Dosage, Side Effects and Interactions

It is a mimetic (cholinergic) parasympathetic bronchoconstrictor agent that is administered in solution only.

The bronchial provocation test is the most widely used and accepted approach for the evaluation of airway hyperresponsiveness.

This common nonspecific provocative agent is used for aerosolized bronchial challenge.

In this test, the patient inhales an aerosol of one or more concentrations of methacholine.

Results from lung function tests such as spirometry and specific conductance, performed before and after inhalations are used to measure response.

Chemical formula

  • C8H18NO2+.


Each 20 ml vial contains 100 mg and each 50 ml vial contains 1,600 mg of methacholine chloride powder which must be reconstituted with an injection of 0.9% sodium chloride or an injection of 0.9% sodium chloride containing 0.4 % phenol, with a pH of 7.


Methacholine is indicated for the diagnosis of bronchial airway hyperresponsiveness in subjects who do not have clinically apparent asthma.

Mechanism of action

Bronchoconstriction occurs when the vagus nerve is stimulated and acetylcholine is released from nerve endings.

Muscle constriction is essentially limited to the local site of release because acetylcholine is rapidly inactivated by acetylcholinesterase.

When a sodium chloride solution containing methacholine chloride is inhaled, individuals with asthma are markedly more sensitive to methacholine-induced bronchoconstriction than healthy subjects.

This difference in response is the pharmacological basis for the methacholine inhalation diagnostic challenge.

However, it should be recognized that methacholine challenge may occasionally be positive after influenza, upper respiratory infections or immunizations, in very young or very old patients, in patients with chronic lung disease such as cystic fibrosis, sarcoidosis , tuberculosis, lung disease chronic obstructive.

The challenge may also be positive in patients with allergic rhinitis without asthma, in smokers, in patients after exposure to air pollutants, or in patients who have had or will develop asthma in the future.


Before the methacholine inhalation test is started, baseline lung function tests should be performed .

A subject to be challenged must have a forced expiratory volume of at least 70% of the predicted value.

The target level for a positive challenge is a 20% reduction in FEV compared to baseline after inhalation of the control sodium chloride solution.

The same diluent as methacholine powder should be used for reference spirometry.

This target value must be calculated and recorded before the methacholine challenge is started.

Side effects

Adverse reactions associated with the use of inhaled methacholine include:

  • Headache.
  • Throat pain.
  • Daze.
  • Sickness.
  • Vomiting or dizziness

Methacholine should be administered by inhalation only.

When administered orally or by injection, methacholine chloride is reported to be associated with substernal pain or pressure, hypotension, fainting, and transient complete heart block.

Report any of the following serious side effects to your doctor immediately: shortness of breath, cough, wheezing, chest pain or tightness, irregular heartbeat.

Warnings and Contraindications

Generally it should not be administered in patients with epilepsy. cardiovascular disease accompanied by bradycardia, vagotonia, diseases such as peptic ulcers, thyroid disease, urinary tract obstruction, or other condition that could be adversely affected by a cholinergic agent.

This test should be performed only if the physician believes that the benefit to the individual outweighs the potential risks.

It is not known whether methacholine can cause fetal harm when administered to a pregnant patient or affect her reproductive capacity.

Methacholine should be given to a pregnant woman only if clearly necessary.

Inhalation stimulation of methacholine should not be administered to a nursing mother, as it is not known whether methacholine chloride when inhaled is excreted in human milk.

The safety and efficacy of the methacholine inhalation challenge have not been established in children under 5 years of age.

Methacholine is contraindicated in patients with known hypersensitivity to this drug or other parasympathetic mimetic agents.

Repeated administration of methacholine by inhalation other than on the day a patient undergoes an escalating dose test is contraindicated.

The inhalation test should not be performed in patients receiving any beta-adrenergic blocking agent because in such patients the responses to methacholine chloride may be exaggerated or prolonged, and they may not respond as readily to accepted treatment modalities.

Before using this medicine, your doctor should be informed if the patient suffers from seizures, heart disease, thyroid-associated diseases, difficulty urinating ( urinary obstruction ).

Also stomach ulcers, seasonal allergies such as allergic rhinitis, having been exposed to air pollutants, recent flu or some other lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, among others.


Acetylcholinesterase inhibitors, when coadministered with methacholine, can potentiate the adverse or toxic effect of cholinergic agonists.

Beta-blockers, when administered together, can potentiate the adverse or toxic effect of methacholine.