◎ Sugi Atlas

Atlas / Drug / Methacholine

Methacholine

drug
On this page

Also known as Methacholine cationMethacholine ionSID90340728

Summary

Methacholine (CHEMBL978) is an approved small-molecule muscarinic agonist (ATC V04CX03) targeting CHRM1, CHRM2, and CHRM3; indicated across 1 condition including asthma.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: V04CX03
  • Targets: 5 (CHRM1, CHRM2, CHRM3…)
  • Indications: 1 condition
  • Clinical trials: 20
  • Chemistry: 160.23 Da · C8H18NO2+

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL978
NameMethacholine
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID1993
ChEBICHEBI:6804
ATCV04CX03
Molecular formulaC8H18NO2+
Molecular weight160.23
InChIKeyNZWOPGCLSHLLPA-UHFFFAOYSA-N

SMILES: CC(C[N+](C)(C)C)OC(=O)C

IUPAC name: 2-acetyloxypropyl(trimethyl)azanium

ChEBI definition: A quaternary ammonium ion in which the nitrogen is substituted with three methyl groups and a 2-acetoxypropyl group. Parasympathomimetic bronchoconstrictor drug used in clinical diagnosis.

Pharmacological roles (ChEBI): muscarinic agonist, bronchoconstrictor agent, epitope, cholinergic agonist, vasodilator agent.

Also known as: Methacholine, Methacholine cation, Methacholine ion, SID90340728, METHACHOLINE, methacholine

Parent form; salt/anhydrous children: CHEMBL12137, CHEMBL1200764, CHEMBL2106885

Patent coverage: 2,986 distinct patent families (10,834 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
CHRM1M1 receptorAgonist6.40.2%P11229
CHRM2M2 receptorAgonist7.230%P08172
CHRM3M3 receptorAgonist6.920%P20309
CHRM4M4 receptorAgonist5.81.6%P08173
CHRM5M5 receptorAgonist0%P08912

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Muscarinic acetylcholine receptor M4, Thromboxane A2 receptor, Muscarinic acetylcholine receptor M2, Muscarinic acetylcholine receptor M1, Muscarinic acetylcholine receptor M1, Muscarinic acetylcholine receptor M2, Muscarinic acetylcholine receptor M4, Muscarinic acetylcholine receptor M3.

Bioactivity

ChEMBL activities: 15 potent at pChembl ≥ 5 of 15 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
CHRM18.1AC507.9nMCHEMBL_ACT_25209604
P109807.23Ki59nMCHEMBL_ACT_1187557
CHRM27.23Ki59nMCHEMBL_ACT_1220390
P084836.92EC50120nMCHEMBL_ACT_1187564
P109806.42IC50380nMCHEMBL_ACT_1187560
CHRM26.42IC50380nMCHEMBL_ACT_1220393
P084826.4EC50400nMCHEMBL_ACT_1187563
P084856.16IC50700nMCHEMBL_ACT_1187562
TBXA2R6.08AC50824.4nMCHEMBL_ACT_25211352
P084855.8Ki1600nMCHEMBL_ACT_1187559
CHRM45.8Ki1600nMCHEMBL_ACT_1220392
CHRM25.66AC502215nMCHEMBL_ACT_25195994
P109805.28IC505200nMCHEMBL_ACT_1187561
CHRM25.28IC505200nMCHEMBL_ACT_1220394
CHRM25.01AC509700nMCHEMBL_ACT_25196390

Target pathways

Aggregated over 5 target gene(s): CHRM1, CHRM2, CHRM3, CHRM4, CHRM5.

Top Reactome pathways

17 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction5CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
Signaling by GPCR5CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
Class A/1 (Rhodopsin-like receptors)5CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
Amine ligand-binding receptors5CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
GPCR downstream signalling5CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
Muscarinic acetylcholine receptors5CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
GPCR ligand binding5CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
G alpha (q) signalling events3CHRM1, CHRM3, CHRM5
G alpha (i) signalling events2CHRM2, CHRM4
Metabolism1CHRM3
Integration of energy metabolism1CHRM3
Membrane Trafficking1CHRM2
Acetylcholine regulates insulin secretion1CHRM3
Regulation of insulin secretion1CHRM3
Vesicle-mediated transport1CHRM2
Cargo recognition for clathrin-mediated endocytosis1CHRM2
Clathrin-mediated endocytosis1CHRM2

Dominant GO biological processes

GO termTargets
signal transduction5
G protein-coupled receptor signaling pathway5
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger5
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway5
G protein-coupled acetylcholine receptor signaling pathway5
chemical synaptic transmission5
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway3
nervous system development3
acetylcholine receptor signaling pathway3
regulation of locomotion2
saliva secretion2
regulation of smooth muscle contraction2
phospholipase C-activating G protein-coupled receptor signaling pathway1
neuromuscular synaptic transmission1
positive regulation of monoatomic ion transport1

Indications & clinical

Indications

1 indication (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
asthma3MONDO:0004979MONDO:0004979

Clinical trials

Total trials: 20.

Phase distribution

PhaseTrials
Not specified14
PHASE34
PHASE42

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01642745PHASE4COMPLETEDMannitol (Aridol) and Methacholine (Provocholine) Responsiveness
NCT02574975PHASE4UNKNOWNAssessment of Airway Responsiveness and Treatment Efficacy in Asthmatics
NCT00252291PHASE3COMPLETEDAbility of Aridol to Detect Bronchial Hyperresponsiveness in Suspected Asthmatics
NCT02097537PHASE3COMPLETEDStudy of Methacholine Chloride Inhalation Challenge in Children With Bronchial Asthma
NCT02100267PHASE3COMPLETEDA Study to Evaluate Efficacy and Safety of Methacholine Chloride Challenge Test in Diagnosis of Adult Asthma
NCT03505489PHASE3COMPLETEDThe Effect of Deep Inhalation on Mannitol Responsiveness
NCT04912596Not specifiedRECRUITINGPharmacodynamic Equivalence of the Test and Reference Metered Dose Inhalers (MDIs) Containing Albuterol Sulfate in Adult Patients With Stable Mild Asthma
NCT06836375Not specifiedNOT_YET_RECRUITINGPilot Study for the Application of Low Power External Bioelectronic Devices in the Diagnosis of Bronchial Asthma.
NCT07288827Not specifiedRECRUITINGExamining Bronchial Hyperresponsiveness in Primary Ciliary Dyskinesia
NCT00145990Not specifiedCOMPLETEDThe Impact of Dosimeter on Measurement of Airway Responsiveness to Methacholine
NCT00513487Not specifiedCOMPLETEDEffects of Multiple Nasal Exposures to House Dust Mite Allergen on Nasal and Body Inflammation and Airway Sensitivity
NCT00890539Not specifiedCOMPLETEDMethacholine Challenge: Comparison of Doubling and Quadrupling Methacholine Dose Regimes Using the Tidal Volume Method
NCT01777867Not specifiedCOMPLETEDCough Reflex Sensitivity and Bronchial Hyper-responsiveness
NCT02026492Not specifiedCOMPLETEDExercise Challenge in a Cold Chamber
NCT02104284Not specifiedCOMPLETEDA Comparative Bronchial Provocation Study With Mannitol and Methacolinie in a Korean Population
NCT02410096Not specifiedCOMPLETEDBronchial Inflammation and Hyperresponsiveness After Oil Supplementation
NCT02502825Not specifiedCOMPLETEDComparison of Methacholine Bronchial Provocation With Wright and Devilbiss646 Nebulizers
NCT02630511Not specifiedCOMPLETEDAsthma Exacerbations and Vascular Function
NCT03825302Not specifiedWITHDRAWNProstaglandin E2 as a Critical Mediator of Sex Disparities in Asthma
NCT04109534Not specifiedUNKNOWNEffect of a Dietary Fatty Acid Supplementation on Symptoms and Bronchial Inflammation in Patients With Asthma

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 3 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

576 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
ACLIDINIUM BROMIDEChEMBL + PubChemPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CLOZAPINEChEMBL + PubChemPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
GENTIAN VIOLETChEMBL + PubChemPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
MavorixaforChEMBL + PubChemPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
OLANZAPINEChEMBL + PubChemPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
ACETYLCHOLINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
AMIODARONEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
AMITRIPTYLINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
AMOXAPINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
ASTEMIZOLEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
ATROPINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
BENZTROPINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
BETHANECHOLChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CARBACHOLChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CARBAMOYLCHOLINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CHLOROQUINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CHLORPROMAZINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CINNARIZINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CLEMASTINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CLIDINIUMChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CLOMIPRAMINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CYCLIZINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CYPROHEPTADINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DARIFENACINChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DESLORATADINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DEXCHLORPHENIRAMINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DICYCLOMINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DIMENHYDRINATEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DIPHENHYDRAMINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DIPHENIDOLChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DOXEPINChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
EBASTINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
GLYCOPYRRONIUM BROMIDEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
HALOPERIDOLChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
HOMATROPINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
HYDROXYCHLOROQUINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
IMIPRAMINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
IPRATROPIUMChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
KETOTIFENChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
LOXAPINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
MAPROTILINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
MEPAZINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
METHSCOPOLAMINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
METHSCOPOLAMINE BROMIDEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
MIANSERINChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
NORTRIPTYLINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
ORPHENADRINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
OXYBUTYNINChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PAROXETINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PERHEXILINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PILOCARPINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PIRENZEPINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PROCHLORPERAZINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PROMAZINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PROMETHAZINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
QUETIAPINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
QUINACRINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
RISPERIDONEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
SCOPOLAMINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
SERTRALINEChEMBLPhase 4 (approved)CHRM1, CHRM2, CHRM3, CHRM4, CHRM5

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot