The muscarinic acetylcholine receptor M₁, 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 Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

) 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 An autonomic ganglion is a cluster of nerve cell bodies (a ganglion) in the autonomic nervous system The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that s ...

* Secretion from salivary glands *

Gastric acid Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the ...

secretion from stomach * In CNS (memory?) * Vagally-induced bronchoconstriction * Mediating

olfactory The sense of smell, or olfaction, is the special sense through which smells (or odors) are perceived. The sense of smell has many functions, including detecting desirable foods, hazards, and pheromones, and plays a role in taste. In humans, it ...

behaviors (e.g.

aggression Aggression is overt or covert, often harmful, social interaction with the intention of inflicting damage or other harm upon another individual; although it can be channeled into creative and practical outlets for some. It may occur either reacti ...

, mating) *Antagonism - delirium hallucinations (the M1 receptor is the only known muscarinic receptor to have this effect as of 2015)

Occurrence in free living amoebae

A structural but not sequential homolog of the human M1 receptor has been reported in ''

Acanthamoeba castellanii ''Acanthamoeba'' is a genus of amoebae that are commonly recovered from soil, fresh water, and other habitats. ''Acanthamoeba'' has two evolutive forms, the metabolically active trophozoite and a dormant, stress-resistant cyst. Trophozoites are ...

'' and '' Naegleria fowleri''. Antagonists of human M1 receptors (e.g.

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...

, 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 The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

Ligands

Agonists

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

carbachol Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. Thus it is classified as a cholinergic agonist. It is primarily used for var ...

cevimeline Cevimeline (trade name Evoxac) is a synthetic analog of the natural alkaloid muscarine with a particular agonistic effect on M1 and M3 receptors. It is used in the treatment of dry mouth and Sjögren's syndrome. Medical uses Cevimeline is us ...

* muscarine * oxotremorine * pilocarpine *

vedaclidine Vedaclidine (INN, codenamed LY-297,802, NNC 11-1053) is an experimental analgesic drug which acts as a mixed agonist–antagonist at muscarinic acetylcholine receptors, being a potent and selective agonist for the M1 and M4 subtypes, yet an ...

* xanomeline *

77-LH-28-1 77-LH-28-1 is a selective agonist of muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and ...

- brain penetrant selective M₁ 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 * sup>3HT-1284- M1-selective PAM Radioligand

Antagonists

* diphenhydramine *

tramadol Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an h ...

* dicycloverine *

fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...

hyoscyamine Hyoscyamine (also known as daturine or duboisine) is a naturally occurring tropane alkaloid and plant toxin. It is a secondary metabolite found in certain plants of the family Solanaceae, including henbane, mandrake, angel's trumpets, jimsonweed ...

ipratropium Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic (SAMA: short acting muscarinic antagonist) medication which opens up the medium and large airways in the lungs. It is used to treat the symptoms ...

mamba toxin Mambas are fast moving highly venomous snakes of the genus ''Dendroaspis'' (which literally means "tree asp") in the family Elapidae. Four extant species are recognised currently; three of those four species are essentially arboreal and green ...

muscarinic toxin 7 Muscarinic toxin 7 (MT7) is one member of a family of small peptides of 65 amino acid residues derived from the venom of African mamba snakes (Dendroaspis angusticeps), which mainly target M1-subtype of muscarinic receptor Muscarinic acetylch ...

(MT7) *Many antipsychotics like olanzapine, quetiapine, clozapine, chlorpromazine *

pirenzepine Pirenzepine (Gastrozepin), an M1 selective antagonist, is used in the treatment of peptic ulcers, as it reduces gastric acid secretion and reduces muscle spasm. It is in a class of drugs known as muscarinic receptor antagonists - acetylcholine ...

* oxybutynin * Benzatropine * telenzepine * paroxetine *Tricyclic and tetracyclic antidepressants like

clomipramine Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used for the treatment of obsessive–compulsive disorder, panic disorder, major depressive disorder, and chronic pain. It may increase th ...

imipramine Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. The drug is also used to treat bedwetting. ...

, mirtazapine, amitriptyline * tolterodine * Biperiden

References

External links

* {{DEFAULTSORT:Muscarinic Acetylcholine Receptor M1 Muscarinic acetylcholine receptors