The muscarinic acetylcholine receptor M₁, also known as the cholinergic receptor, muscarinic 1, is a

muscarinic receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...

that in humans is encoded by the ''CHRM1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. It is localized to 11q13. This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve, is common in

exocrine gland Exocrine glands are glands that secrete substances onto an epithelial surface by way of a duct. Examples of exocrine glands include sweat, salivary, mammary, ceruminous, lacrimal, sebaceous, prostate and mucous. Exocrine glands are one of ...

s and in the CNS. It is predominantly found bound to G proteins of class G_q that use upregulation of

phospholipase C Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role i ...

and, therefore,

inositol trisphosphate Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the ...

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: Areas of confinement, imprisonment, or for execution * Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups * Extermination ...

) 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 neuron, nerve cell Cell body, bodies (a ganglion) in the autonomic nervous system. The two types are the sympathetic ganglion and the parasympathetic ganglion. References

Autonomic ganglia, Auto ...

* Secretion from

salivary gland The salivary glands in many vertebrates including mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of min ...

s *

Gastric acid Gastric acid or stomach acid is the acidic component – hydrochloric acid – of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. In humans, the pH is between one and three, much lower than most other a ...

secretion from

stomach The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...

* Via the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

(especially within the brain); mediating certain core aspects of

perception Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous syste ...

, attention, cognitive functioning and likely;

memory consolidation Memory consolidation is a category of processes that stabilize a memory trace after its initial acquisition. A memory trace is a change in the nervous system caused by memorizing something. Consolidation is distinguished into two specific processe ...

. This is a notable component in regards to the M₁ receptor since it helps explain how pharmacological compounds which antagonize the receptor site can consistently produce mental states like

delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...

(a major disruption in attention and decrease in baseline-level cognitive functioning), as well as the perceptual alterations and conspicuous

hallucinations A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

experienced with ''

deliriant Deliriants are a subclass of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelics such as LSD and dissociatives such as ketamine, due to their primary effect of causing delirium, as opposed to th ...

'' drugs like ''

Datura ''Datura'' is a genus of nine species of highly poisonous, Vespertine (biology), vespertine-flowering plants belonging to the nightshade family (Solanaceae). They are commonly known as thornapples or jimsonweeds, but are also known as devil's t ...

''. As of 2015, the M₁ receptor remains the only known muscarinic receptor to have this effect of hallucinogenic delirium when its functionality is inhibited or antagonized. *

Cognitive flexibility Cognitive flexibility is an intrinsic property of a cognitive system often associated with the mental ability to adjust its activity and content, switch between different task rules and corresponding behavioral responses, maintain multiple con ...

Synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to Chemical synapse#Synaptic strength, strengthen or weaken over time, in response to increases or decreases in their activity. Since memory, memories are postulated to be represent ...

modulation * Anxiety-like behavior and spontaneous working memory * Task switching * Vagally-induced

bronchoconstriction Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. Causes The condition has a number of causes, the most common bei ...

* 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 and detection of "social odors" which have implications (for rodents) in

aggression Aggression is behavior aimed at opposing or attacking something or someone. Though often done with the intent to cause harm, some might channel it into creative and practical outlets. It may occur either reactively or without provocation. In h ...

mating In biology, mating is the pairing of either opposite-sex or hermaphroditic organisms for the purposes of sexual reproduction. ''Fertilization'' is the fusion of two gametes. '' Copulation'' is the union of the sex organs of two sexually repr ...

, and

social behavior Social behavior is behavior among two or more organisms within the same species, it encompasses any behavior in which one member affects another. Social behavior can be seen as similar to an exchange of goods, with the expectation that when you ...

Occurrence in free living amoebae

A structural but not sequential

homolog In biology, homology is similarity in anatomical structures or genes between organisms of different taxa due to shared ancestry, ''regardless'' of current functional differences. Evolutionary biology explains homologous structures as retained her ...

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. The genus ''Acanthamoeba'' has two stages in its life cycle, the metabolically active trophozoite stage and a dormant, stress-resistan ...

'' and ''

Naegleria fowleri ''Naegleria fowleri'', also known as the brain-eating amoeba, is a species of the genus ''Naegleria''. It belongs to the phylum Percolozoa and is classified as an amoeboflagellate Excavata, excavate, an organism capable of behaving as both an ...

''. 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 give ...

diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

) 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, carboxy 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 t ...

Ligands

Agonists

Acetylcholine Acetylcholine (ACh) is an organic compound 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. Par ...

Arecoline Arecoline is a cholinergic agent, stimulant, and natural product, naturally occurring alkaloid found in areca nut, areca (betel) nuts of the areca palm (''Areca catechu'') found in South Asia, South and Southeast Asia. Its effects, depending on ...

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 v ...

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 u ...

* Itameline *

Muscarine Muscarine, L-(+)-muscarine, or muscarin is a Secondary metabolite, natural product found in certain mushrooms, particularly in ''Inocybe'' and ''Clitocybe'' species, such as the deadly ''Clitocybe dealbata, C. dealbata''. Mushrooms in the g ...

Oxotremorine Oxotremorine is a drug that acts as a selective muscarinic acetylcholine receptor agonist. Oxotremorine produces ataxia, tremor and spasticity, similar to those symptoms seen in Parkinsonism, and has thus become a research tool in experimental s ...

Pilocarpine Pilocarpine, sold under the brand name Pilopine HS among others, is a lactone alkaloid originally extracted from plants of the Pilocarpus genus. It is used as a medication to reduce pressure inside the eye and treat dry mouth. As an eye drop ...

* Vedaclidine *

Xanomeline Xanomeline (developmental code name LY-246,708) is a small molecule muscarinic acetylcholine receptor agonist that was synthesized in a collaboration between Eli Lilly and Novo Nordisk as an investigational therapeutic being studied for the tre ...

* 77-LH-28-1 - 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

* BQCA * BQZ-12 * VU-0090157 * VU-0029767 * VU0467319 * sup>3HT-1284- M1-selective PAM Radioligand

Antagonists

scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin a ...

tramadol Tramadol, sold under the brand name Tramal among others, is an opioid analgesic, pain medication and a serotonin–norepinephrine reuptake inhibitor (SNRI) used to treat moderately severe pain. When taken by mouth in an immediate-release form ...

dicycloverine Dicycloverine, also known as dicyclomine, sold under the brand name Bentyl among others, is a medication that is used to treat spasms of the intestines such as those that occur in irritable bowel syndrome (IBS). It is taken by mouth or by injec ...

fluoxetine Fluoxetine, sold under the brand name Prozac, among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used for the treatment of major depressive disorder, Anxiety disorder, anx ...

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 Hyoscyamus niger, henbane, Mandragora officina ...

ipratropium Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons. The inhalant opens up the medium ...

mamba toxin Mambas are fast-moving, highly Venomous snake, venomous snakes of the genus ''Dendroaspis'' (which literally means "tree Asp (reptile), asp") in the family Elapidae. Four Neontology, extant species are recognised currently; three of those four s ...

muscarinic toxin 7 (MT7) * Many antipsychotics like

olanzapine Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomitin ...

quetiapine Quetiapine ( ), sold under the brand name Seroquel among others, is an atypical antipsychotic medication used in the treatment of schizophrenia, bipolar disorder, bipolar depression, and major depressive disorder. Despite being widely prescri ...

clozapine Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily to treat people with schizophrenia and schizoaffective disorder who have ...

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar d ...

* pirenzepine *

oxybutynin Oxybutynin, sold under the brand name Ditropan among others, is an anticholinergic medication primarily used to treat overactive bladder. It is widely considered a first-line therapy for overactive bladder due to its well-studied side effect ...

Benzatropine Benzatropine ( INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is n ...

telenzepine Telenzepine is a thienobenzodiazepine acting as selective M1 antimuscarinic. It is used in the treatment of peptic ulcers. Telenzepine is atropisomer Atropisomers are stereoisomers arising because of hindered rotation about a covalent bond, ...

paroxetine Paroxetine ( ), sold under the brand name Paxil among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, obsessive-compulsive disorder, o ...

* PIPE-359 * Tricyclic and tetracyclic antidepressants like

clomipramine Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most notably obsessive–compulsive disorder but also many other disorders, including hyper ...

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. Imipramine is taken by mouth. Common s ...

mirtazapine Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant, atypical tetracyclic antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks but ca ...

amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, and a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headac ...

tolterodine Tolterodine, sold under the brand name Detrol among others, is a medication used to treat frequent urination, urinary incontinence, or urinary urgency. Effects are seen within an hour. It is taken by mouth. Common side effects include head ...

Biperiden Biperiden, sold under the brand name Akineton among others, is a medication used to treat Parkinson disease, certain drug-induced movement disorders and Tourette Syndrome. It is not recommended for tardive dyskinesias. It is taken by mouth, in ...

References

External links

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