# Muscarinic acetylcholine receptor M1

The muscarinic acetylcholine receptor M$_1$, also known as the cholinergic receptor, muscarinic 1, is a muscarinic receptor that in humans is encoded by the CHRM1 gene. It is localized to 11q13.
This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve, is common in exocrine glands and in the CNS.
It is predominantly found bound to G proteins of class G$_q$ that use upregulation of phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signalling pathway. A receptor so bound would not be susceptible to CTX or PTX. However, G$_i$ (causing a downstream decrease in cAMP) and G$_s$ (causing an increase in cAMP) have also been shown to be involved in interactions in certain tissues, and so would be susceptible to PTX and CTX respectively.

## Effects

* EPSP in autonomic ganglia
* Secretion from salivary glands
* Gastric acid secretion from stomach
* Via the central nervous system (especially within the brain); mediating certain core aspects of perception, attention, cognitive functioning and likely; memory consolidation. This is a notable component in regards to the M$_1$ receptor since it helps explain how pharmacological compounds which antagonize the receptor site can consistently produce mental states like delirium (a major disruption in attention and decrease in baseline-level cognitive functioning), as well as the perceptual alterations and conspicuous hallucinations experienced with deliriant drugs like Datura. As of 2015, the M$_1$ receptor remains the only known muscarinic receptor to have this effect of hallucinogenic delirium when its functionality is inhibited or antagonized.
* Cognitive flexibility
* Synaptic plasticity modulation
* Anxiety-like behavior and spontaneous working memory
* Salivation
* Task switching
* Vagally-induced bronchoconstriction
* Mediating olfactory behaviors and detection of "social odors" which have implications (for rodents) in aggression, mating, and social behavior.

## Occurrence in free living amoebae

A structural but not sequential homolog of the human M1 receptor has been reported in Acanthamoeba castellanii and Naegleria fowleri. Antagonists of human M1 receptors (e.g. atropine, diphenhydramine) have been shown to exert anti-proliferative effects on these pathogens.

## Mechanism

It couples to G$_q$, and, to a small extent, G$_i$ and G$_s$. This results in slow EPSP and decreased K$^+$ conductance. It is preassembled to the G$_q$ heterotrimer through a polybasic c-terminal domain.

## Ligands
### Agonists

* Acetylcholine
* Arecoline
* Carbachol
* Cevimeline
* Itameline
* Muscarine
* Oxotremorine
* Pilocarpine
* Vedaclidine
* Xanomeline
* 77-LH-28-1 - brain penetrant selective M$_1$ allosteric agonist
* CDD-0097
* McN-A-343 - mixed M1/M4 agonist
* L-689, L-660 - mixed M1/M3 agonist

### Allosteric modulators

* benzylquinolone carboxylic acid
* BQZ-12
* VU-0090157
* VU-0029767
* VU0467319
* [$^3$H]PT-1284- M1-selective PAM Radioligand

### Antagonists

* atropine
* diphenhydramine
* scopolamine
* tramadol
* dicycloverine
* fluoxetine
* hyoscyamine
* ipratropium
* mamba toxin muscarinic toxin 7 (MT7)
* Many antipsychotics like olanzapine, quetiapine, clozapine, chlorpromazine
* pirenzepine
* oxybutynin
* Benzatropine
* telenzepine
* paroxetine
* Tricyclic and tetracyclic antidepressants like clomipramine, imipramine, mirtazapine, amitriptyline
* tolterodine
* Biperiden