Acetylcholine Muscarinic Receptors

Muscarinic receptors are widely distributed throughout the body and control distinct functions according to location and subtype (M1 - M5).They are predominantly expressed in the parasympathetic nervous system where they exert both inhibitory and excitatory effects.

Targets
Literature
Receptor Data

Acetylcholine Muscarinic Receptor Target Files

Muscarinic receptor agonists and antagonists could prove useful in the research and treatment of a wide range of central nervous system diseases including Alzheimer's disease and Parkinson's disease.

The table below summarizes the properties of muscarinic receptors and includes affinity values of some key muscarinic receptor-selective ligands available from Tocris.

Literature for Acetylcholine Muscarinic Receptors

Cardiovascular

Cardiovascular Research Product Guide

A collection of over 250 products for cardiovascular research, the guide includes research tools for the study of:

  • Hypertension
  • Thrombosis and Hemostasis
  • Atherosclerosis
  • Myocardial Infarction
  • Ischemia/Reperfusion Injury
  • Arrhythmias
  • Heart Failure
GPCR

GPCR Product Listing

A collection of over 450 products for G protein-coupled receptors, the listing includes research tools for the study of:

  • Rhodopsin-like Receptors
  • Secretin-like Receptors
  • Glutamate Receptors
  • Frizzled Receptors
  • GPCR Signaling
Pain

Pain Research Product Guide

A collection of over 250 products for pain research, the guide includes research tools for the study of:

  • Nociception
  • Ion Channels
  • G-Protein-Coupled Receptors
  • Intracellular Signaling
Alzheimer's

Alzheimer's Poster

Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia, affecting approximately 47 million people worldwide. Updated in 2015, this poster summarizes the structural and functional changes observed in the progression of this neurodegenerative disease, as well as classic AD drug targets.

Cardiovascular

Cardiovascular Poster

Cardiovascular disease remains one of the major causes of morbidity and mortality in the Western world and therefore this therapeutic area continues to be of great interest to researchers. This poster highlights the key GPCRs regulating vascular reactivity.

Learning & Memory

Learning & Memory Poster

Recognition memory enables us to make judgements about whether or not we have encountered a particular stimulus before. This poster outlines the cellular mechanisms underlying recognition memory and its links to long-term depression, as well as the use of pharmacological intervention to assess the role of neurotransmitters in recognition memory.

Schizophrenia

Schizophrenia Poster

Schizophrenia is a debilitating psychiatric disorder that affects 1% of the worldwide population. This poster highlights the targets and pathways representing the most promising strategies to pursue for novel drug development.

Muscarinic Receptor Pharmacological Data

Receptor Subtype M1 M2 M3 M4 M5
Transduction Mechanism ↑PLC (Gq/11) ↓Adenylyl Cyclase (Gi/o) ↑PLC (Gq/11) ↓Adenylyl Cyclase (Gi/o) ↑PLC (Gq/11)
Primary Distribution Neocortex, hippocampus, neostriatum, salivary glands, eye, heart Brain, heart, smooth muscle, salivary glands Smooth muscle, exocrine glands, brain, autonomic ganglia, salivary glands Neostriatum, cortex, hippocampus, autonomic ganglia Substantia nigra, pars compacta, ventral tegmental area, hippocampus
Tissue Function Learning and memory, neuromodulation, M-current inhibition Bradycardia, smooth muscle contraction, antinociception, hyperthermia, ↓ neurotransmitter release (presynaptic) Smooth muscle contraction, gland secretion, ↓ neurotransmitter release (presynaptic) Regulation of dopamine D1 stimulated locomotor activity Unknown
Key Compounds pKB Values
Agonists Oxotremorine (0843)
Oxotremorine M (1067)
Pilopcarpine (0694)
923*
20286*
4718†
70*
107*
-
881*
8299*
2796†
454*
975*
-
-
-
2476†
Antagonists AF-DX 116 (1105)
AF-DX 384 (1345)
AQ-RA 741 (2292)
4-DAMP (0482)
(S)-(+)-Dimethindene (1425)
J 104129 (2507)
PD 102807 (1671)
Pirenzepine (1071)
J 104129 (2507)
Zamifenacin (2579)
417*
7.5
29*
8.6-9.2
7.08‡
19
5.3
8.5
19*
7.90‡
64-73*
8.2-9.0
3.7*
8.4
7.78‡
490
5.7
6.7
490*
7.93‡
786*
7.8
55*
9.3
6.70‡
4.2
6.2
7.1
4.2*
8.52‡
211*
8.0-8.7
1.5*
8.4-9.4
7.00‡
-
7.3
8.1
-
7.78‡
5130*
6.3
732*
8.9-9.0
-
-
5.2
7.1
-
-

* Ki values, ‡ pKi values, † EC50 value

References

Caulfield and Birdshall (1998) International union of pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol.Rev. 50 279. Mansfield et al (2005) Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT-PCR: changes in ageing. Br.J.Pharmacol. 144 1089. Pfaff et al (1995) The (S)-(+)-enantiomer of dimethindene: a novel M2-selective muscarinic receptor antagonist. Eur.J.Pharmacol. 286 229. Loudon et al (1997) SB 202026: a novel muscarinic partial agonist with functional selectivity for M1 receptors. J.Pharmacol.Exp.Ther. 283 1059. Burstein et al (1997) Pharmacology of muscarinic receptor subtypes constitutively activated by G proteins. Mol.Pharmacol. 51 312. Mitsuya et al (2000) Discovery of a muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors among 2-[(1S,2S)-3-sulfonylaminocyclopentylacetamide derivatives. Bioorg.Med.Chem. 8 825. Watson et al (1995) Characterization of the interaction of zamifenacin at muscarinic receptors in vitro. Eur.J.Pharmacol. 285 135. Mitsuya et al J-104129, a novel muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors. Bioorg.Med.Chem.Lett. 7 2555.