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. Medical uses
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. 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 to 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 identical to acetylcholine but with a methyl group on the beta carbon (hence being called acetyl-β-methylcholine), this β-methyl group provides selectivity towards muscarinic receptors as compared to nicotinic receptors. The quaternary ammonium group is essential for activity. The ester makes it susceptible to the enzyme acetylcholine esterase. Contraindications
Use of methacholine is contraindicated in patients with recent heart attack or stroke, uncontrolled hypertension, known severe airway disease, or an aortic aneurysm.
According to clinical practice guidelines, for newborns found to have bilateral inaccessible gonads, CAH evaluation should be considered. If virilizing CAH cannot be identified and treated, both boys and girls may undergo rapid postnatal growth and virilization. Nonclassic
In addition to the salt-wasting and simple-virilizing forms of CAH diagnosed in infancy,  a mild or "nonclassic" form exists, which is characterized by varying degrees of postnatal androgen excess, but is sometimes asymptomatic. The nonclassic form may be noticed in late childhood and may lead to accelerated growth, premature sexual maturation, acne, and secondary polycystic ovary syndrome. In adult males, early balding and infertility may suggest the diagnosis. The nonclassic form is characterized by mild subclinical impairment of cortisol synthesis; serum cortisol concentration is usually normal. Signs and symptoms
The symptoms of CAH vary depending upon the form of CAH and the sex of the patient. Symptoms can include:
Due to inadequate mineralocorticoids:
Vomiting due to salt-wasting, leading to dehydration and deathDue to excess androgens:

In extreme virilization, an elongated clitoris with a phallic-like structure is seen. Ambiguous genitalia, in some infants, occurs such that initially identifying  external genitalia as "male" or "female" is difficult. Early pubic hair and rapid growth occurs in childhood. Precocious puberty or failure of puberty to occur (sexual infantilism: absent or delayed puberty)
Excessive facial hair, virilization, and/or menstrual irregularity in adolescence
Infertility due to anovulation
Clitoromegaly, enlarged clitoris and shallow vaginaDue to insufficient androgens and estrogens:
Undervirilization in XY males can result in apparently female external genitalia.