Provocholine

Provocholine Uses, Dosage, Side Effects, Food Interaction and all others data.

Asthma is a complex condition associated with phenomena such as airway hyperresponsiveness (AHR), in which the smooth muscle in the airways (ASM) excessively contracts in response to stimuli, reducing pulmonary function and causing symptoms such as difficulty breathing. Although the underlying pathology of AHR is complex, ASM contraction can be stimulated by cholinergic agonists that activate M3 muscarinic receptors that stimulate ASM contraction. Provocholine is a non-specific cholinergic agonist (parasympathomimetic) that acts through muscarinic receptors in the lungs to induce bronchoconstriction. In patients with AHR, a lower dose of methacholine is required to induce bronchoconstriction, which forms the basis for the methacholine challenge test to diagnose AHR.

Provocholine was granted FDA approval on October 31, 1986, and is marketed under the trademark PROVOCHOLINE® by Methapharm Inc.

Provocholine is a non-specific cholinergic agonist (parasympathomimetic) that acts through muscarinic receptors in the lungs to induce bronchoconstriction, which is more significant in patients with asthma than those without. Therefore, methacholine carries a risk of severe bronchoconstriction, especially in patients with pre-existing reduced pulmonary function (typically baseline FEV1 < 60% or < 1.5 L, at least in adults), clinically apparent asthma or wheezing, or other health conditions such as uncontrolled hypertension, aortic aneurysm, or history of myocardial infarction or stroke. Use in patients with epilepsy, vagotonia, peptic ulcer disease, thyroid disease, urinary tract obstruction or other conditions that could be adversely affected by a cholinergic agent is not recommended. Also, there is a potential risk to healthcare workers administering the methacholine challenge test; proper precautions and protective equipment should be used as needed.

Provocholine
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Uses during Pregnancy
Uses during Breastfeeding
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Trade Name	Provocholine
Availability	Prescription only
Generic	Methacholine
Methacholine Other Names	Acetyl-beta-methylcholine, Acetylmethylcholine, beta-Methylacetylcholine, Methacholine, Methacholinum
Related Drugs	glucagon, mannitol, Tubersol, arginine, inulin
Type	Inhalation
Formula	C₈H₁₈NO₂
Weight	Average: 160.234 Monoisotopic: 160.133753825
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States,
Last Updated:	September 19, 2023 at 7:00 am

Uses

Provocholine is a parasympathomimetic bronchoconstrictor used to diagnose bronchial hyperreactivity in subjects who do not have clinically apparent asthma.

Provocholine is indicated in adult and pediatric patients aged five years and older without clinically apparent asthma for the diagnosis of bronchial airway hyperactivity via the methacholine challenge test.

Provocholine is also used to associated treatment for these conditions: Bronchial airway hyperreactivity

How Provocholine works

Asthma is a complicated condition associated with airway remodelling, including the proliferation of airway smooth muscle (ASM) and altered extracellular matrix, aberrant pro-inflammatory immune responses, and excessive ASM contraction leading to decreased lung function. Excessive ASM contraction in response to contractile agonists, a phenomenon termed airway hyperresponsiveness (AHR), is a physical manifestation of the altered pulmonary physiology in asthma. Although numerous factors, such as increased ASM levels, pro-contractile molecules, pro-inflammatory cytokines, and growth factors, contribute to AHR, one of the key factors in determining ASM tone is regulated by vagal parasympathetic nerve innervation. The response to acetylcholine and other cholinergic agonists at these neuromuscular junctions is predominantly controlled by inhibitory G_i-coupled M₂ and excitatory G_q-coupled M₃ muscarinic acetylcholine receptors (mAChRs). Activation of M₃ receptors results in ASM contraction and resulting bronchoconstriction through downstream calcium-dependent signalling pathways, while M₂ activation inhibits neuronal acetylcholine release.

Provocholine is a non-specific mAChR agonist, capable of acting on all mAChR subtypes. However, in the context of AHR, methacholine's ability to induce bronchoconstriction through M₃ receptors is clinically relevant. In addition, M₃ agonism may increase the release of pro-inflammatory cytokines, further contributing to AHR. The inhibitory effect of M₂ agonism by methacholine is likely also important, as shown by animal studies using mice with impaired M₂ function, and by observations that eosinophilic inflammation, such as occurs in asthma, negatively impacts M₂ function. Hence, asthmatic patients are more sensitive to inhaled cholinergic agonists such as methacholine; this forms the basis for the methacholine challenge test, which diagnoses AHR through an increased methacholine-induced response.