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.