Muscarinic acetylcholine receptor M4

The muscarinic acetylcholine receptor M4, also known as the cholinergic receptor, muscarinic 4 (CHRM4), is a is_associated_with::protein that, in humans, is encoded by the CHRM4 is_associated_with::gene.

Function
M4 is_associated_with::muscarinic receptors are coupled to Gi/o heterotrimeric proteins.

It function as inhibitory is_associated_with::autoreceptors for acetylcholine. Activation of M4 receptors inhibits is_associated_with::acetylcholine release in the is_associated_with::striatum. The M2 subtype of acetylcholine receptor functions similarly as an inhibitory autoreceptor to acetylcholine release, albeit functioning actively primarily in the is_associated_with::hippocampus and is_associated_with::cerebral cortex.

is_associated_with::Muscarinic acetylcholine receptors possess a regulatory effect on is_associated_with::dopaminergic is_associated_with::neurotransmission. Activation of M4 receptors in the is_associated_with::striatum inhibit D1-induced locomotor stimulation in is_associated_with::mice. M4 receptor-deficient mice exhibit increased locomotor simulation in response to D1 agonists, is_associated_with::amphetamine and is_associated_with::cocaine. Neurotransmission in the striatum influences extrapyramidal is_associated_with::motor control, thus alterations in M4 activity may contribute to conditions such as is_associated_with::Parkinson's Disease.

Orthosteric agonists

 * is_associated_with::acetylcholine
 * is_associated_with::carbachol
 * is_associated_with::oxotremorine



Positive allosteric modulators

 * LY-2033298
 * is_associated_with::VU-0152100 (ML-108)
 * VU-0152099

Antagonists

 * is_associated_with::AFDX-384 (mixed M2/M4 antagonist, N-[2-[2-[(Dipropylamino)methyl]-1-piperidinyl]ethyl]-5,6-dihydro-6-oxo-11H-pyrido[2,3-b][1,4]benzodiazepine-11-carboxamide, CAS# 118290-27-0)
 * is_associated_with::Dicycloverine
 * is_associated_with::Himbacine
 * is_associated_with::Mamba toxin 3
 * is_associated_with::PD-102,807 (3,6a,11,14-Tetrahydro-9-methoxy-2-methyl-(12H)-isoquino[1,2-b]pyrrolo[3,2-f][1,3]benzoxazine-1-carboxylic acid ethyl ester, CAS# 23062-91-1)
 * is_associated_with::PD-0298029
 * is_associated_with::Tropicamide - moderate selectivity over other muscarinic subtypes (2-5x approx)