Muscarinic acetylcholine receptors (mAChRs) are

acetylcholine receptor An acetylcholine receptor (abbreviated AChR) or a cholinergic receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter. Classification Like other transmembrane receptors, acetylcholine receptor ...

s that form G protein-coupled receptor complexes in the

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

s of certain

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

and other

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

s. They play several roles, including acting as the main end-receptor stimulated by

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 ...

released from postganglionic fibers. They are mainly found in the

parasympathetic nervous system The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The autonomic nervous system is responsible for regulat ...

, but also have a role in the

sympathetic nervous system The sympathetic nervous system (SNS or SANS, sympathetic autonomic nervous system, to differentiate it from the somatic nervous system) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous sy ...

in the control of

sweat glands Sweat glands, also known as sudoriferous or sudoriparous glands, , are small tubular structures of the skin that produce sweat. Sweat glands are a type of exocrine gland, which are glands that produce and secrete substances onto an epithelial sur ...

. Muscarinic receptors are so named because they are more sensitive to

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 ...

than to

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

. Their counterparts are

nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...

s (nAChRs), receptor ion channels that are also important in the

autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...

. Many drugs and other substances (for example

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 ...

and

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 ...

) manipulate these two distinct receptors by acting as selective

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

s or

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.

Function

Acetylcholine (ACh) is a

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

found in the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

neuromuscular junctions A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...

and the

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 ...

. Muscarinic receptors are used in the following roles:

Recovery receptors

ACh is always used as the

within the

autonomic ganglion An autonomic ganglion is a cluster of nerve cell bodies (a ganglion) in the autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of ...

. Nicotinic receptors on the postganglionic neuron are responsible for the initial fast depolarization (Fast EPSP) of that neuron. As a consequence of this, nicotinic receptors are often cited as ''the receptor on the postganglionic neurons at the ganglion''. However, the subsequent hyperpolarization (

IPSP An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Incorporated; 2008. ...

) and slow depolarization (Slow EPSP) that represent the recovery of the postganglionic neuron from stimulation are actually mediated by ''muscarinic'' receptors, types M₂ and M₁ respectively (discussed below). Peripheral autonomic fibers (sympathetic and parasympathetic fibers) are categorized anatomically as either preganglionic or

postganglionic fiber In the autonomic nervous system, nerve fibers from the ganglion to the effector organ are called postganglionic nerve fibers. Neurotransmitters The neurotransmitters of postganglionic fibers differ: * In the parasympathetic division, neurons ...

s, then further generalized as either adrenergic fibers, releasing noradrenaline, or cholinergic fibers, both releasing acetylcholine and expressing acetylcholine receptors. Both preganglionic sympathetic fibers and preganglionic parasympathetic fibers are cholinergic. Most postganglionic sympathetic fibers are adrenergic: their neurotransmitter is norepinephrine except postganglionic sympathetic fibers to the sweat glands, piloerectile muscles of the body hairs, and the skeletal muscle arterioles do not use adrenaline/noradrenaline. The

adrenal medulla The adrenal medulla () is the inner part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cells that secrete catecho ...

is considered a sympathetic ganglion and, like other sympathetic ganglia, is supplied by cholinergic preganglionic sympathetic fibers: acetylcholine is the neurotransmitter utilized at this synapse. The

chromaffin cells Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to stress, monito ...

of the adrenal medulla act as "modified neurons", releasing adrenaline and noradrenaline into the bloodstream as hormones instead of as neurotransmitters. The other postganglionic fibers of the peripheral autonomic system belong to the parasympathetic division; all are cholinergic fibers, and use acetylcholine as the neurotransmitter.

Postganglionic neurons

Another role for these receptors is at the junction of the innervated tissues and the postganglionic neurons in the parasympathetic division of the autonomic nervous system. Here acetylcholine is again used as a neurotransmitter, and ''muscarinic'' receptors form the principal receptors on the innervated tissue.

Innervated tissue

Very few parts of the sympathetic system use cholinergic receptors. In sweat glands the receptors are of the ''muscarinic'' type. The sympathetic nervous system also has some preganglionic nerves terminating at the

chromaffin cell Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the adrenal medulla, medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to ...

s in the

, which secrete

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

into the bloodstream. Some believe that chromaffin cells are modified postganglionic CNS fibers. In the adrenal medulla, acetylcholine is used as a neurotransmitter, and the receptor is of the ''nicotinic'' type. The

somatic nervous system The somatic nervous system (SNS), also known as voluntary nervous system, is a part of the peripheral nervous system (PNS) that links brain and spinal cord to skeletal muscles under conscious control, as well as to sensory receptors in the skin ...

uses a nicotinic receptor to acetylcholine at the neuromuscular junction.

Higher central nervous system

Muscarinic acetylcholine receptors are also present and distributed throughout the local nervous system, in post-synaptic and pre-synaptic positions. There is also some evidence for

postsynaptic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

receptors on sympathetic neurons allowing the parasympathetic nervous system to inhibit sympathetic effects.

Presynaptic membrane of the neuromuscular junction

It is known that muscarinic acetylcholine receptors also appear on the pre-synaptic membrane of somatic neurons in the neuro-muscular junction, where they are involved in the regulation of acetylcholine release.

Form of muscarinic receptors

Muscarinic acetylcholine receptors belong to a class of

metabotropic receptor A metabotropic receptor, also referred to by the broader term G-protein-coupled receptor, is a type of membrane receptor that initiates a number of metabolic steps to modulate cell activity. The nervous system utilizes two types of receptors: me ...

s that use

G protein G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell (biology), ...

s as their signaling mechanism. In such receptors, the signaling molecule (the

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

) binds to a monomeric

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

that has seven transmembrane regions; in this case, the ligand is ACh. This receptor is bound to intracellular proteins, known as G proteins, which begin the information cascade within the cell. By contrast, nicotinic receptors form pentameric complexes and use a

ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as sodium, Na+, potassium, K+, calcium, Ca2+, and/or chloride, Cl− to ...

mechanism for signaling. In this case, binding of the ligands with the receptor causes an

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

to open, permitting either one or more specific types of ions (e.g., K⁺, Na⁺, Ca²⁺) to diffuse into or out of the cell.

Receptor isoforms

Classification

By the use of selective radioactively labeled agonist and antagonist substances, five subtypes of muscarinic receptors have been determined, named M₁–M₅ (using an upper case M and subscript number). M₁, M₃, M₅ receptors are coupled with G_q proteins, while M₂ and M₄ receptors are coupled with G_i/o proteins. There are other classification systems. For example, the drug pirenzepine is a muscarinic antagonist (decreases the effect of ACh), which is much more potent at M₁ receptors than it is at other subtypes. The acceptance of the various subtypes proceeded in numerical order, therefore, earlier sources may recognize only M₁ and M₂ subtypes, while later studies recognize M₃, M_{4
and most recently M₅ subtypes.

Genetic differences

Meanwhile, geneticist

A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic process ...
s and molecular biologist

Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
s have characterised five genes that appear to encode muscarinic receptors, named m1-m5 (lowercase m; no subscript number). They code for pharmacologic types M₁-M₅. The receptors m1 and m2 were determined based upon partial sequencing of M₁ and M₂ receptor proteins. The others were found by searching for homology, using bioinformatic

Bioinformatics () is an interdisciplinary field of science

Science is a systematic discipline that builds and organises knowledge in the form of testable hypotheses and predictions about the universe. Modern science is typically divi ...
techniques.

Difference in G proteins

G proteins contain an alpha-subunit that is critical to the functioning of receptors. These subunits can take a number of forms. There are four broad classes of form of G-protein: G_s, G_i, G_q, and G_12/13. Muscarinic receptors vary in the G protein to which they are bound, with some correlation according to receptor type. G proteins are also classified according to their susceptibility to cholera toxin

Cholera toxin (also known as choleragen, CTX, CTx and CT) is a potent enterotoxin produced by the bacterium Vibrio cholerae which causes severe watery diarrhea and dehydration that define cholera infections. The toxin is a member of the heat-l ...
(CTX) and pertussis toxin

Pertussis toxin (PT) is a protein-based AB5-type exotoxin produced by the bacterium '' Bordetella pertussis'', which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection. ...
(PTX, whooping cough). G_s and some subtypes of G_i (G_αt and G_αg) are susceptible to CTX. Only G_i is susceptible to PTX, with the exception of one subtype of G_i (G_αz) which is immune. Also, only when bound with an agonist, those G proteins normally sensitive to PTX also become susceptible to CTX.

The various G-protein subunits act differently upon secondary messengers, upregulating Phospholipases, downregulating cAMP, and so on.

Because of the strong correlations to muscarinic receptor type, CTX and PTX are useful experimental tools in investigating these receptors.

The muscarinic acetylcholine receptor subtype sectivities of a large number of antimuscarinic drugs have been reviewed.

M₁ receptor

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, which use upregulation of phospholipase

A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C, and D, which are distinguished by the type of reaction which they catalyze:

*Phospholipase ...
C 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 signaling 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.

M₂ receptor

The M₂ muscarinic receptors are located in the heart and lungs. In the heart, they act to slow the heart rate

Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...
down below the normal baseline sinus rhythm

A sinus rhythm is any cardiac rhythm in which depolarisation of the cardiac muscle begins at the sinus node. It is necessary, but not sufficient, for normal electrical activity within the heart. On the electrocardiogram (ECG), a sinus rhythm ...
, by slowing the speed of depolarization

In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...
. In humans, under resting conditions, vagal activity dominates over sympathetic activity. Hence, inhibition of M₂ receptors (e.g. by atropine) will cause a raise in heart rate. They also moderately reduce contractile forces of the atrial

The atrium (; : atria) is one of the two upper chambers in the heart that receives blood from the circulatory system. The blood in the atria is pumped into the heart ventricles through the atrioventricular mitral and tricuspid heart valves.
...
cardiac muscle

Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...
, and reduce conduction velocity of the atrioventricular node

The atrioventricular node (AV node, or Aschoff-Tawara node) electrically connects the heart's atria and ventricles to coordinate beating in the top of the heart; it is part of the electrical conduction system of the heart. The AV node lies at the ...
(AV node). It also serves to slightly decrease the contractile forces of the ventricular muscle.

M₂ muscarinic receptors act via a G_i type receptor, which causes a decrease in cAMP in the cell, inhibition of voltage-gated Ca²⁺ channels, and increasing efflux of K⁺, in general, leading to inhibitory-type effects.

M₃ receptor

The M₃ muscarinic receptors are located at many places in the body. They are located in the smooth muscles of the blood vessels, as well as in the lungs. Because the M₃ receptor is G_q-coupled and mediates an increase in intracellular calcium, it typically causes contraction of smooth muscle, such as that observed during 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 ...
and bladder voiding. However, with respect to vasculature, activation of M₃ on vascular endothelial cells causes increased synthesis of nitric oxide

Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...
, which diffuses to adjacent vascular smooth muscle cells and causes their relaxation, thereby explaining the paradoxical effect of parasympathomimetic

A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs becaus ...
s on vascular tone and bronchiolar tone. Indeed, direct stimulation of vascular smooth muscle, M₃ mediates vasoconstriction in diseases wherein the vascular endothelium is disrupted.
The M₃ receptors are also located in many glands, which help to stimulate secretion in, for example, the salivary glands, as well as other glands of the body.

Like the M₁ muscarinic receptor, M₃ receptors are G proteins of class G_q that upregulate 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 signaling pathway.

M₄ receptor

M₄ receptors are found in the CNS. M₄ receptors are also located in erythroid progenitor cell

A progenitor cell is a biological cell that can differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor cells. Progenitor cells can only diffe ...
in peripheral tissue and modulate the cAMP pathway to regulate erythroid progenitor cell differentiation. Therapies targeting the M₄ receptor treats myelodysplastic syndrome

A myelodysplastic syndrome (MDS) is one of a group of cancers in which blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may includ ...
and anemia

Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
that are refractory to erythropoietin

Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...
.

M₄ receptors work via G_i receptors to decrease cAMP in the cell and, thus, produce generally inhibitory effects. Possible bronchospasm

Bronchospasm or a bronchial spasm is a sudden bronchoconstriction, constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylat ...
may result if stimulated by muscarinic agonist

A muscarinic acetylcholine receptor agonist, also simply known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, lab ...
s.

M₅ receptor

Location of M₅ receptors is not well known.

Like the M₁ and M₃ muscarinic receptor, M₅ receptors are coupled with G proteins of class G_q that upregulate phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signaling pathway.

Pharmacological application

Ligands

In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...
targeting the mAChR that are currently approved for clinical use include non-selective antagonists for the treatment of Parkinson's disease

Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
, 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 ...
(to dilate the pupil

The pupil is a hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black becau ...
), 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 ...
(used to prevent motion sickness

Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include ...
), and 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 ...
(used in the treatment of COPD

Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...
).

In 2024, the United States FDA approved the drug KarXT (Cobenfy), which is a combination drug that combines xanomeline (a preferentially acting M1/M4 muscarinic acetylcholine receptor agonist) with trospium (a peripherally-restricted pan-mAChR antagonist for use in schizophrenia. In early clinical trials of moderate to high severity patients without treatment resistant history, it has demonstrated efficacy about equivalent to that of other anti-psychotics (20-point improvement in PANSS vs 10-point placebo improvement), with a notably different side effect profile (very low rates of metabolic effects, hypotension, weight changes, or EPS) with moderately reported rates of nausea and constipation. No trials have been published to date regarding use in combination with other antipsychotics, use in treatment resistant patients, or head-to-head comparisons with other medications. This is the first anti-psychotic drug approved that uses a muscarinic mechanism of action, and many others are in development.

See also

* Muscarinic agonist

A muscarinic acetylcholine receptor agonist, also simply known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, lab ...

* Muscarinic antagonist

A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...

* Acetylcholine receptor

An acetylcholine receptor (abbreviated AChR) or a cholinergic receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.
Classification
Like other transmembrane receptors, acetylcholine receptor ...
(Cholinergic receptor)
:* Nicotinic acetylcholine receptor

Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...

* Adrenergic receptor

The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like b ...

* Nicotinic agonist
A nicotinic agonist is a drug that mimics the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs). The nAChR is named for its affinity for nicotine.

Examples include nicotine (by definition), acetylcholine (the endogenous a ...

* Nicotinic antagonist
* Vagal escape

References

External links

Acetylcholine Receptors (Muscarinic)
*

{{DEFAULTSORT:Muscarinic Acetylcholine Receptor

Neurochemistry
Neurophysiology
Acetylcholine receptors}

Function

Recovery receptors

Postganglionic neurons

Innervated tissue

Higher central nervous system

Presynaptic membrane of the neuromuscular junction

Form of muscarinic receptors

Receptor isoforms

Classification

Genetic differences

Difference in G proteins

M1 receptor

M2 receptor

M3 receptor

M4 receptor

M5 receptor

Pharmacological application

See also

References

External links

M₁ receptor

M₂ receptor

M₃ receptor

M₄ receptor

M₅ receptor