Muscarinic acetylcholine receptor M5

The human muscarinic acetylcholine receptor M5, encoded by the gene, is a member of the is_associated_with::G protein-coupled receptor superfamily of is_associated_with::integral membrane proteins. It is coupled to Gq protein. Binding of the is_associated_with::endogenous ligand is_associated_with::acetylcholine to the M5 receptor triggers a number of cellular responses such as is_associated_with::adenylate cyclase inhibition, is_associated_with::phosphoinositide degradation, and is_associated_with::potassium channel modulation. Muscarinic receptors mediate many of the effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor have not been fully explored; however, stimulation of this receptor is known to effectively decrease is_associated_with::cyclic AMP levels and downregulate the activity of protein kinase A (PKA).

Ligands
No highly selective agonists or antagonists for the M5 receptor have been discovered as of 2009, but several non-selective muscarinic agonists and antagonists have significant affinity for M5.

The lack of selective M5 receptor ligands is one of the main reasons that the medical community has such a limited understanding of the M5 receptors effects as the possibility that any and/or all effects of non-selective ligands may be due to interactions with other receptors can not be ruled out. Some data may be obtained by observing which effects are common among semi-selective ligands (ex. a ligand of M1 and M5, a ligand of M2 and M5, and a ligand of M3 and M5), but until both a selective agonist and a selective antagonist of the M5 receptor are developed this data must be considered merely theoretical.

Agonists

 * is_associated_with::Milameline ((E)-1,2,5,6-Tetrahydro-1-methyl-3-pyridinecarboxaldehyde-O-methyloxime, CAS# 139886-32-1)
 * is_associated_with::Sabcomeline

Positive allosteric modulators

 * ML-380
 * ML-326
 * is_associated_with::VU-0238429: EC50 = 1.16 μM; >30-fold selectivity versus M1 and M3, inactive at M2 and M4.

Negative allosteric modulators

 * is_associated_with::ML375

Antagonists

 * VU-0488130 (ML381)
 * is_associated_with::Xanomeline