The human muscarinic acetylcholine receptor M₅ which is encoded by the gene is a member of the G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

 superfamily of integral membrane protein

Integral membrane protein

An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...

s. Binding of the endogenous

Endogenous

Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

 ligand

Ligand (biochemistry)

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...

 acetylcholine

Acetylcholine

The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 to the M₅ receptor triggers a number of cellular responses such as adenylate cyclase

Adenylate cyclase

Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....

 inhibition, phosphoinositide degradation, and potassium channel

Potassium channel

In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...

 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 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.

Agonists

• Milameline
  Milameline
  Milameline is a non-selective muscarinic acetylcholine receptor partial agonist with cognition-acting properties that was being investigated for the treatment of Alzheimer's disease, but produced poor results in clinical trials and was subsequently discontinued....
  
   ((E)-1,2,5,6-Tetrahydro-1-methyl-3-pyridinecarboxaldehyde-O-methyloxime, CAS# 139886-32-1)
• Sabcomeline
  Sabcomeline
  Sabcomeline is a selective M1 receptor partial agonist that was under development for the treatment of Alzheimer's disease. It made it to phase III clinical trials before being discontinued due to poor results....
  
  

Positive allosteric modulators

• VU-0238429
  VU-0238429
  VU-0238429 is a drug which acts as a selective positive allosteric modulator for the muscarinic acetylcholine receptor M5. It was the first selective ligand developed for the M5 subtype, and is structurally derived from older M1-selective positive allosteric modulators such as VU-0119498....
  
  : EC₅₀ = 1.16 μM; >30-fold selectivity versus M1 and M3, inactive at M2 and M4.

Further reading