Protein / target

Muscarinic acetylcholine receptor M3

CHRM3P20309Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
59
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Phosphatidylinositol-4,5-bisphosphate phospholipase C activity

Primary system

Nervous system

Strongest disease association

prune belly syndrome

Genetic literature evidence · score 0.80

Therapeutic maturity

Clinically validated target

59 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

59 approved · 12 in clinical development

30 linked trials

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

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.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Pilocarpine
Narrow target profileApprovedAgonist

Muscarinic acetylcholine receptor M3 agonist

Appears in clinical studies involving xerostomia, Sjogren syndrome, angle-closure glaucoma, Miosis

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

prune belly syndrome0.80

Genetic literature · overall 0.70

Hyperhidrosis0.48

Genetic · overall 0.63

seasonal allergic rhinitis0.48

Genetic · overall 0.62

gastrointestinal disease0.47

Genetic · overall 0.66

chronic obstructive pulmonary disease0.41

Genetic · overall 0.67

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

overactive bladder1.00

Clinical · overall 0.61

asthma0.99

Clinical · overall 0.61

Urinary incontinence0.98

Clinical · overall 0.60

urgency urinary incontinence0.98

Clinical · overall 0.59

pulmonary emphysema0.97

Clinical · overall 0.59

Show all associations
prune belly syndrome0.70
chronic obstructive pulmonary disease0.67
gastrointestinal disease0.66
Hyperhidrosis0.63
seasonal allergic rhinitis0.62
overactive bladder0.61
asthma0.61
Urinary incontinence0.60
urgency urinary incontinence0.59
pulmonary emphysema0.59

Open Targets ranks 1,981 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 72 total

GLYCOPYRRONIUM TOSYLATEApproval

peptic ulcer disease · cardiac arrhythmia · Hyperhidrosis

ISOPROPAMIDE IODIDEApproval

allergic rhinitis

BETHANECHOL CHLORIDEApproval

Urinary retention

CARBACHOLApproval

Miosis · cataract · glaucoma

DAROTROPIUM BROMIDEPhase 2

chronic obstructive pulmonary disease

PROPANTHELINEApproval

gastrointestinal disease · Hyperhidrosis

TALSACLIDINEPhase 2 3
HEXOCYCLIUMApproval

gastrointestinal disease

UMECLIDINIUM BROMIDEApproval

pulmonary emphysema · chronic obstructive pulmonary disease · chronic bronchitis

PROPANTHELINE BROMIDEApproval

peptic ulcer disease · overactive bladder

Tractability

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

Safety liabilities

acidosisexhaustiondry mouthblurred visionabdominal crampsconstipationincreased/decreased blood pressureincreased body temperatureurinary smooth muscle constrictionbronchoconstrictionfrothingdecreased salivation

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.

Show remaining trials (24)

COMPLETED · via Pilocarpine · NCT01690052

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

chronic obstructive pulmonary diseaseWell 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

HyperhidrosisWell supported
0.84
agreement 0.730.95
Clinical59%Genetic41%Literature0%

Open Targets aggregate 0.63 · 3 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

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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

4

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  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 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.