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.
Acetylcholine Muscarinic Receptor Targets
M1 Receptors (M1 Receptors) | M4 Receptors (M4 Receptors) |
M2 Receptors (M2 Receptors) | M5 Receptors (M5 Receptors) |
M3 Receptors (M3 Receptors) |
Related Targets
Acetylcholine Nicotinic Receptors | Hydroxycarboxylic Acid Receptors (Hydroxycarboxylic Acid Receptors) |
Cholinesterases (Cholinesterases) | Non-selective Muscarinics |
DREADD Ligands |
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.
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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 |
| Featured 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) | 417* 7.5 29* 8.6-9.2 7.08‡ 19 5.3 8.5 19* | 64-73* 8.2-9.0 3.7* 8.4 7.78‡ 490 5.7 6.7 490* | 786* 7.8 55* 9.3 6.70‡ 4.2 6.2 7.1 4.2* | 211* 8.0-8.7 1.5* 8.4-9.4 7.00‡ - 7.3 8.1 - | 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.