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Protein / target

Muscarinic acetylcholine receptor M3

Encoded byCHRM3P20309Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
59
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Phosphatidylinositol-4,5-bisphosphate phospholipase C

Strongest disease association

Prune belly syndrome

Via encoding gene CHRM3 · Genetic literature evidence · score 0.80

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins.

View complete UniProt function annotation

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Subcellular location

Cell membranePostsynaptic cell membraneBasolateral cell membraneEndoplasmic reticulum membrane
Domains and Gene Ontology detail (25)

Gene Ontology

  • Cbasal plasma membrane
  • Cbasolateral plasma membrane
  • Cdendrite
  • Cendoplasmic reticulum membrane
  • Cplasma membrane
  • Cpostsynaptic membrane
  • Csynapse
  • Facetylcholine binding
  • FG protein-coupled acetylcholine receptor activity
  • Fphosphatidylinositol-4,5-bisphosphate phospholipase C activity
  • Fsignaling receptor activity
  • Pacetylcholine receptor signaling pathway

590 aa · 66 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingUniProt · GOG protein-coupled signallingGOMuscle contractionGO
View supporting evidence

Synaptic signalling

  • ·Postsynaptic cell membrane
  • ·postsynaptic membrane
  • ·synapse
  • ·chemical synaptic transmission

G protein-coupled signalling

  • ·G protein-coupled acetylcholine receptor activity
  • ·adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway
  • ·G protein-coupled acetylcholine receptor signaling pathway
  • ·G protein-coupled receptor signaling pathway

Muscle contraction

  • ·positive regulation of smooth muscle contraction
  • ·regulation of smooth muscle contraction
View underlying pathways (3)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

GNAQCHRM5GRM5GNG12CHRM1GNA11KNG1GNA15AGTRAPGNALCHRM3

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

2 medicines · 9 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Glaucoma1 medicine
Glaucoma, Angle-Closure1 medicine
Glaucoma, Open-Angle1 medicine
Ocular Hypertension1 medicine
Sjogren's Syndrome1 medicine
Urinary Bladder, Overactive1 medicine
Urinary Incontinence1 medicine
Urinary Incontinence, Urge1 medicine
Xerostomia1 medicine

59 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Pilocarpine
Narrow target profileApprovedAgonist

Muscarinic acetylcholine receptor M3 agonist

Indicated for Glaucoma, Glaucoma, Angle-Closure, Glaucoma, Open-Angle, Ocular Hypertension

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

oxybutynin
Narrow target profileApprovedAntagonist

Muscarinic acetylcholine receptor M3 antagonist

Indicated for Urinary Bladder, Overactive, Urinary Incontinence, Urinary Incontinence, Urge

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CHRM3

Gene-level evidence surfaced through the gene CHRM3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Pulmonary Disease, Chronic Obstructive
0.85Well supported

Clinical evidence dominant · Open Targets 0.67

Gastrointestinal disease
0.85Well supported

Clinical evidence dominant · Open Targets 0.66

Seasonal allergic rhinitis
0.83Well supported

Clinical evidence dominant · Open Targets 0.62

Prune belly syndrome
0.78Well supported

Genetic evidence dominant · Open Targets 0.70

Urinary Bladder, Overactive
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

View evidence synthesis (5)
Pulmonary Disease, Chronic ObstructiveWell supported
0.85
agreement 0.750.96
Clinical63%Genetic35%Literature2%

Open Targets aggregate 0.67 · 3 independent evidence families

Gastrointestinal diseaseWell supported
0.85
agreement 0.750.95
Clinical60%Genetic40%

Open Targets aggregate 0.66 · 2 independent evidence families

Seasonal allergic rhinitisWell supported
0.83
agreement 0.730.94
Clinical59%Genetic42%

Open Targets aggregate 0.62 · 2 independent evidence families

Prune belly syndromeWell supported
0.78
agreement 0.660.90
Genetic87%Animal model13%Literature1%Genetic literaturedup

Open Targets aggregate 0.70 · 3 independent evidence families · 1 not counted as duplicate

Urinary Bladder, OveractiveWell supported
0.75
agreement 0.600.91
Clinical98%Literature2%

Open Targets aggregate 0.61 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Prune belly syndrome0.70
Pulmonary Disease, Chronic Obstructive0.67
Gastrointestinal disease0.66
Seasonal allergic rhinitis0.62
Urinary Bladder, Overactive0.61
Asthma0.61
Urinary Incontinence, Urge0.59
Pulmonary Emphysema0.59

Drug development

72 compounds recorded · 59 approved · 12 in clinical development · 1 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
GLYCOPYRRONIUM TOSYLATEApproval
ISOPROPAMIDE IODIDEApproval
BETHANECHOL CHLORIDEApproval
CARBACHOLApproval
DAROTROPIUM BROMIDEPhase 2
PROPANTHELINEApproval
TALSACLIDINEPhase 2 3
HEXOCYCLIUMApproval
UMECLIDINIUM BROMIDEApproval
PROPANTHELINE BROMIDEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (11)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

acidosisLynch et al. (2017)exhaustionLynch et al. (2017)dry mouthBowes et al. (2012)blurred visionBowes et al. (2012)abdominal crampsLynch et al. (2017)constipationLynch et al. (2017)increased/decreased blood pressureLynch et al. (2017)increased body temperatureLynch et al. (2017)urinary smooth muscle constrictionBowes et al. (2012)bronchoconstrictionBowes et al. (2012)frothingLynch et al. (2017)decreased salivationLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

UNKNOWN · via Pilocarpine · NCT02982577

COMPLETED · via oxybutynin · NCT01310712

COMPLETED · via oxybutynin · NCT03877289

UNKNOWN · via Pilocarpine · NCT05578001

COMPLETED · via oxybutynin · NCT02538302

ClinicalTrials.gov via the drug-target graph.

What's happening now

6

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. New publication2024-04-16
    A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure.

    Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024 · 14 citations · Europe PMC · via Pilocarpine

  2. New publication2012-01-17
    Phase 2 results from Radiation Therapy Oncology Group Study 0537: a phase 2/3 study comparing acupuncture-like transcutaneous electrical nerve stimulation versus pilocarpine in treating early radiation-induced xerostomia.

    Cancer · 2012 · 34 citations · Europe PMC · via Pilocarpine

  3. New publication2011-05-01
    A phase III randomized, double-blind, placebo-controlled study of pilocarpine for vaginal dryness: North Central Cancer Treatment group study N04CA.

    The journal of supportive oncology · 2011 · 9 citations · Europe PMC · via Pilocarpine

  4. New publication2009-08-15
    Efficacy and safety of transdermal and oral oxybutynin in children with neurogenic detrusor overactivity.

    The Journal of urology · 2009 · 14 citations · Europe PMC · via oxybutynin

  5. Regulatory approval2004-06-15

    Approval: Kentera (previously Oxybutynin Nicobrand) (EMA)

    ema · regulatory · ema · via oxybutynin

  6. New publication1997-05-01
    Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus.

    The Journal of neuroscience : the official journal of the Society for Neuroscience · 1997 · 1,402 citations · Europe PMC · via Pilocarpine

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.