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Prestwick3_000759
Also known as: Acetylmethylcholine, 55-92-5, Beta-methylacetylcholine, Acetyl-beta-methylcholine, Methacholine ion, Mch; mecholin
Molecular Formula
C8H18NO2+
Molecular Weight
160.23  g/mol
InChI Key
NZWOPGCLSHLLPA-UHFFFAOYSA-N
FDA UNII
03V657ZD3V

A quaternary ammonium parasympathomimetic agent with the muscarinic actions of ACETYLCHOLINE. It is hydrolyzed by ACETYLCHOLINESTERASE at a considerably slower rate than ACETYLCHOLINE and is more resistant to hydrolysis by nonspecific CHOLINESTERASES so that its actions are more prolonged. It is used as a parasympathomimetic bronchoconstrictor agent and as a diagnostic aid for bronchial asthma. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1116)
Methacholine is a Cholinergic Receptor Agonist. The mechanism of action of methacholine is as a Cholinergic Agonist.
1 2D Structure

Prestwick3_000759

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
2-acetyloxypropyl(trimethyl)azanium
2.1.2 InChI
InChI=1S/C8H18NO2/c1-7(11-8(2)10)6-9(3,4)5/h7H,6H2,1-5H3/q+1
2.1.3 InChI Key
NZWOPGCLSHLLPA-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CC(C[N+](C)(C)C)OC(=O)C
2.2 Other Identifiers
2.2.1 UNII
03V657ZD3V
2.3 Synonyms
2.3.1 MeSH Synonyms

1. 2-(acetyloxy)-n,n,n-trimethyl-1-propanaminium Chloride

2. Acetyl 2 Methylcholine Chloride

3. Acetyl Beta Methacholine Chloride

4. Acetyl Beta Methylcholine

5. Acetyl-2-methylcholine Chloride

6. Acetyl-beta-methacholine Chloride

7. Acetyl-beta-methylcholine

8. Chloride, Methacholine

9. Mecholine

10. Mecholyl

11. Methacholine Chloride

12. Provocholine

13. Provokit

2.3.2 Depositor-Supplied Synonyms

1. Acetylmethylcholine

2. 55-92-5

3. Beta-methylacetylcholine

4. Acetyl-beta-methylcholine

5. Methacholine Ion

6. Mch; Mecholin

7. Methacholine Cation

8. Mecholin

9. Chebi:6804

10. Methacholin

11. Mecholine

12. 03v657zd3v

13. Methacholinum

14. Choline, Acetyl-beta-methyl-

15. Brn 1769932

16. Unii-03v657zd3v

17. 1-propanaminium, 2-(acetyloxy)-n,n,n-trimethyl-

18. Prestwick0_000759

19. Prestwick1_000759

20. Prestwick2_000759

21. Prestwick3_000759

22. Chembl978

23. Cid_6114

24. Methacholine [vandf]

25. Lopac0_000025

26. Schembl69103

27. Bspbio_000778

28. Bspbio_001985

29. Methacholine [who-dd]

30. Spbio_002717

31. Bpbio1_000856

32. Gtpl7438

33. Dtxsid2046967

34. Bdbm48918

35. 2-acetyloxypropyl-trimethylazanium

36. Ammonium, (2-hydroxypropyl)trimethyl-, Acetate (ester)

37. Pdsp1_000136

38. Pdsp2_000135

39. [2-(acetyloxy)propyl]trimethylazanium

40. Ccg-204121

41. Db06709

42. Ncgc00015045-03

43. Ncgc00015045-04

44. Ncgc00015045-06

45. Ncgc00015045-13

46. Ncgc00089798-02

47. 2-acetoxypropyl(trimethyl)ammonium;chloride

48. Sbi-0050014.p003

49. 2-acetyloxy-n,n,n-trimethylpropan-1-aminium

50. 2-acetyloxypropyl(trimethyl)ammonium;chloride

51. C07471

52. Q413188

53. 1-propanaminium, 2-(acetyloxy)-n,n,n-trimethyl-, (+/-)-

2.4 Create Date
2004-09-16
3 Chemical and Physical Properties
Molecular Weight 160.23 g/mol
Molecular Formula C8H18NO2+
XLogP30.6
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count2
Rotatable Bond Count4
Exact Mass160.133753817 g/mol
Monoisotopic Mass160.133753817 g/mol
Topological Polar Surface Area26.3 Ų
Heavy Atom Count11
Formal Charge1
Complexity138
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 2  
Drug NameProvocholine
PubMed HealthMethacholine (By breathing)
Drug ClassesDiagnostic Agent, Bronchial
Drug LabelProvocholine (methacholine chloride powder for inhalation) is a parasympathomimetic (cholinergic)) bronchoconstrictor agent to be administered in solution only, by inhalation, for diagnostic purposes. Each 20 mL vial contains 100 mg of methacholine...
Active IngredientMethacholine chloride
Dosage FormFor solution
RouteInhalation
Strength100mg/vial
Market StatusPrescription
CompanyMethapharm

2 of 2  
Drug NameProvocholine
PubMed HealthMethacholine (By breathing)
Drug ClassesDiagnostic Agent, Bronchial
Drug LabelProvocholine (methacholine chloride powder for inhalation) is a parasympathomimetic (cholinergic)) bronchoconstrictor agent to be administered in solution only, by inhalation, for diagnostic purposes. Each 20 mL vial contains 100 mg of methacholine...
Active IngredientMethacholine chloride
Dosage FormFor solution
RouteInhalation
Strength100mg/vial
Market StatusPrescription
CompanyMethapharm

4.2 Drug Indication

Methacholine 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.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Methacholine 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.


5.2 MeSH Pharmacological Classification

Bronchoconstrictor Agents

Agents causing the narrowing of the lumen of a bronchus or bronchiole. (See all compounds classified as Bronchoconstrictor Agents.)


Miotics

Agents causing contraction of the pupil of the eye. Some sources use the term miotics only for the parasympathomimetics but any drug used to induce miosis is included here. (See all compounds classified as Miotics.)


Muscarinic Agonists

Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. (See all compounds classified as Muscarinic Agonists.)


Parasympathomimetics

Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here. (See all compounds classified as Parasympathomimetics.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
METHACHOLINE
5.3.2 FDA UNII
03V657ZD3V
5.3.3 Pharmacological Classes
Established Pharmacologic Class [EPC] - Cholinergic Receptor Agonist
5.4 ATC Code

V - Various

V04 - Diagnostic agents

V04C - Other diagnostic agents

V04CX - Other diagnostic agents

V04CX03 - Methacholine


5.5 Mechanism of Action

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 Gi-coupled M2 and excitatory Gq-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. Methacholine 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.


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