In neurochemistry, a muscarinic receptor antagonist is an agent that reduces the activity of the muscarinic acetylcholine receptor

Muscarinic acetylcholine receptor

Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...

. Acetylcholine (often abbreviated ACh) is a neurotransmitter, whose receptor is a protein found in synapse

Synapse

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

s and other cell membranes. Besides responding to their primary neurochemical, neurotransmitter receptors can be sensitive to a variety of other molecules. Acetylcholine receptors are classified into two groups based on this:

• muscarinic, which respond to muscarine
  Muscarine
  Muscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested...
  
  
• nicotinic, which respond to nicotine
  Nicotine
  Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
  
  

Most muscarinic receptor antagonists are synthetic, but scopolamine

Scopolamine

Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants, such as henbane, jimson weed and Angel's Trumpets , and corkwood...

 and atropine

Atropine

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...

 are belladonna alkaloids, and are naturally extracted.

Effects

Scopolamine and atropine have similar effects on the peripheral nervous system, however, scopolamine has greater effects on the CNS than atropine due to its ability to cross the blood-brain barrier. At higher than therapeutic doses, atropine and scopolamine cause CNS depression characterized by amnesia, fatigue and reduction in rapid eye movement sleep. Hyoscine has anti-emetic activity, so is used for motion sickness

Motion sickness

Motion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...

.

Antimuscarinics are also used as anti-parkinsonian drugs. In Parkinsonism

Parkinson's disease

Parkinson's disease is a degenerative disorder of the central nervous system...

, there is imbalance between levels of acetylcholine

Acetylcholine

The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 and dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the brain, involving both increased levels of acetylcholine and degeneration of dopaminergic

Dopaminergic

Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...

 pathways (nigrostriatal pathway

Nigrostriatal pathway

The nigrostriatal pathway is a neural pathway that connects the substantia nigra with the striatum. It is one of the four major dopamine pathways in the brain, and is particularly involved in the production of movement, as part of a system called the basal ganglia motor loop.Loss of dopamine...

). Thus, in Parkinsonism there is decreased level of dopaminergic activity. One method of balancing the neurotransmitters is through blocking central cholinergic activity using muscarinic receptor antagonists.

Atropine acts on the M2 receptors of the heart and antagonizes the activity of acetylcholine. It causes tachycardia

Tachycardia

Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

 by blocking vagal effects on the sinoatrial node

Sinoatrial node

The sinoatrial node is the impulse-generating tissue located in the right atrium of the heart, and thus the generator of normal sinus rhythm. It is a group of cells positioned on the wall of the right atrium, near the entrance of the superior vena cava...

. Acetylcholine hyperpolarizes the sinoatrial node which is overcome by MRA and thus increases the heart rate. If atropine is given by intramuscular or subcutaneous injection it causes initial bradycardia

Bradycardia

Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

. This is because by i.m/s.c it acts on presynaptic M1 receptors (autoreceptor

Autoreceptor

An autoreceptor is a receptor located on presynaptic nerve cell membranes and serves as a part of a feedback loop in signal transduction. It is sensitive only to those neurotransmitters or hormones that are released by the neuron in whose membrane the autoreceptor sits.Canonically, a presynaptic...

s). Intake of acetylcholine in axoplasm

Axoplasm

Axoplasm is the cytoplasm within the axon of a neuron. Neural processes contain about 99.6% of the cell’s cytoplasm, and 99.7% of that is in the axons....

 is prevented and the presynaptic nerve releases more acetylcholine into the synapse

Chemical synapse

Chemical synapses are specialized junctions through which neurons signal 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 system. They are crucial to the biological computations that underlie...

 which initially causes bradycardia.

In the atrioventricular node

Atrioventricular node

The atrioventricular node is a part of the electrical control system of the heart that coordinates heart rate. It electrically connects atrial and ventricular chambers...

, the resting potential

Resting potential

The relatively static membrane potential of quiescent cells is called the resting membrane potential , as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential....

 is abbreviated which facilitates conduction. This is seen as a shortened PR-interval on an electrocardiogram

Electrocardiogram

Electrocardiography is a transthoracic interpretation of the electrical activity of the heart over a period of time, as detected by electrodes attached to the outer surface of the skin and recorded by a device external to the body...

.

It has an opposite effect on blood pressure

Blood pressure

Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

. Tachycardia and stimulation of the vasomotor center

Vasomotor center

The vasomotor center is a portion of the medulla oblongata that regulates blood pressure and other homeostatic processes. Upon blood increase in carbon dioxide it stimulates the sympathetic system to constrict vessels. This is opposite to carbon dioxide in tissues causing vasoconstriction,...

 causes an increase in blood pressure. But due to feed back regulation of the vasomotor center, there is fall in blood pressure due to vasodilation

Vasodilation

Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...

.

Important muscarinic antagonists include atropine

Atropine

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...

, hyoscine, ipratropium

Ipratropium

Ipratropium bromide is an anticholinergic drug used for the treatment of chronic obstructive pulmonary disease and acute asthma. It blocks the muscarinic acetylcholine receptors in the smooth muscles of the bronchi in the lungs, opening the bronchi...

, tropicamide

Tropicamide

Tropicamide is an anticholinergic used as a mydriatic. In Russia, it is used to some degree as an inexpensive recreational drug...

, cyclopentolate

Cyclopentolate

Cyclopentolate is a mydriatic and cycloplegic agent commonly used during pediatric eye examinations. Cyclopentolate is also administered as an atropine substitute to reverse muscarinic and CNS effects of indirect cholinomimetic administration....

 and pirenzepine

Pirenzepine

Pirenzepine 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 being the neurotransmitter of the parasympathetic nervous system which initiates the...

.

Comparison table

Substance	Trade names	Mechanism	Clinical use	Adverse effects
Atropine Atropine Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...  (D/L-Hyoscyamine Hyoscyamine Hyoscyamine is a tropane alkaloid. It is a secondary metabolite found in certain plants of the Solanaceae family, including henbane , mandrake , jimsonweed , tomato and deadly nightshade... )		non-selective antagonism, CNS stimulation	in anaesthesia anticholinesterase poisoning bradycardia Bradycardia Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart... antispasmodic Antispasmodic An antispasmodic is a drug or a herb that suppresses muscle spasms.-Smooth muscle spasm:One type of antispasmodics is used for smooth muscle contraction, especially in tubular organs of the gastrointestinal tract...  in gastrointestinal hypermotility	urinary retention Urinary retention Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications... xerostomia Xerostomia Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or... blurred vision Blurred vision -Causes:There are many causes of blurred vision:* Use of atropine or other anticholinergics* Presbyopia -- Difficulty focusing on objects that are close. The elderly are common victims....
Scopolamine Scopolamine Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants, such as henbane, jimson weed and Angel's Trumpets , and corkwood...  (L-Hyoscine)	Scopace, Transderm-Scop, Maldemar, Buscopan	non-selective antagonism, CNS depression	as atropine motion sickness Motion sickness Motion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...	as atropine sedation Sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
Ipratropium Ipratropium Ipratropium bromide is an anticholinergic drug used for the treatment of chronic obstructive pulmonary disease and acute asthma. It blocks the muscarinic acetylcholine receptors in the smooth muscles of the bronchi in the lungs, opening the bronchi...	Atrovent and Apovent	non-selective antagonism, without any mucociliary excretion inhibition.	in asthma Asthma Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...  and bronchitis Bronchitis Acute bronchitis is an inflammation of the large bronchi in the lungs that is usually caused by viruses or bacteria and may last several days or weeks. Characteristic symptoms include cough, sputum production, and shortness of breath and wheezing related to the obstruction of the inflamed airways...
Tropicamide Tropicamide Tropicamide is an anticholinergic used as a mydriatic. In Russia, it is used to some degree as an inexpensive recreational drug...		short acting non-selective antagonism, CNS depression	produce mydriasis Mydriasis Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...  and cycloplegia Cycloplegia Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation.-Anatomy:The iris is the heavily pigmented colored part of the eye. It has a contractile diaphragm in front of the lens with a central opening called the pupil...  in diagnostics	may cause ocular hypertension Ocular hypertension Ocular hypertension is intraocular pressure higher than normal in the absence of optic nerve damage or visual field loss.Current consensus in ophthalmology defines normal introcular pressure as that between 10 mmHg and 21 mmHg...
Pirenzepine Pirenzepine Pirenzepine 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 being the neurotransmitter of the parasympathetic nervous system which initiates the...		M1 receptor-selective antagonist inhibits gastric secretion	in peptic ulcer Peptic ulcer A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...  (not much anymore)	(fewer than non-selective ones)
Diphenhydramine Diphenhydramine Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...	Benadryl Benadryl Benadryl is a brand name allergy medicine marketed over-the-counter by Johnson & Johnson subsidiary McNeil Consumer Healthcare. Prior to 2007, Benadryl was marketed by Pfizer Consumer Healthcare...		for extrapyramidal Extrapyramidal Extrapyramidal can refer to:* Extrapyramidal system* Extrapyramidal symptoms...  symptoms from typical antipsychotic Antipsychotic An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...  medications antihistamine sleep aid
Dimenhydrinate Dimenhydrinate Dimenhydrinate is an over-the-counter drug used to prevent nausea and motion sickness...	Dramamine		motion sickness Motion sickness Motion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...
Dicyclomine Dicyclomine Dicyclomine, also known as dicycloverine, is an anticholinergic that blocks muscarinic receptors. Dicycloverine was first synthesized in the United States circa 1947.- Clinical uses :...
Flavoxate Flavoxate Flavoxate is an anticholinergic with antimuscarinic effects. Its muscle relaxant properties may be due to a direct action on the smooth muscle rather than by antagonizing muscarinic receptors.- Clinical uses :...
Oxybutynin Oxybutynin Oxybutynin is an anticholinergic medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination , by decreasing muscle spasms of the bladder. It competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine...	Ditropan		overactive bladder Overactive bladder Overactive bladder is a urological condition defined by a set of symptoms: urgency, with or without urge incontinence, usually with frequency and nocturia. Frequency is usually defined as urinating more than 8 times a day. The International Continence Society is responsible for this definition... urge incontinence Urge incontinence Urge incontinence is a form of urinary incontinence.Urge incontinence is involuntary loss of urine occurring for no apparent reason while feeling urinary urgency, a sudden need or urge to urinate.-Causes:...
Tiotropium Tiotropium Tiotropium bromide is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease . Tiotropium bromide capsules for inhalation are co-promoted by Boehringer-Ingelheim and Pfizer under the trade name Spiriva...	Spiriva		Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
Cyclopentolate Cyclopentolate Cyclopentolate is a mydriatic and cycloplegic agent commonly used during pediatric eye examinations. Cyclopentolate is also administered as an atropine substitute to reverse muscarinic and CNS effects of indirect cholinomimetic administration....		short acting non-selective antagonism, CNS depression	produce mydriasis Mydriasis Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...  and cycloplegia Cycloplegia Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation.-Anatomy:The iris is the heavily pigmented colored part of the eye. It has a contractile diaphragm in front of the lens with a central opening called the pupil...  in diagnostics	may cause ocular hypertension Ocular hypertension Ocular hypertension is intraocular pressure higher than normal in the absence of optic nerve damage or visual field loss.Current consensus in ophthalmology defines normal introcular pressure as that between 10 mmHg and 21 mmHg...
Atropine methonitrate		non-selective antagonism, blocks transmission in ganglia. Lacks CNS effects	antispasmodic Antispasmodic An antispasmodic is a drug or a herb that suppresses muscle spasms.-Smooth muscle spasm:One type of antispasmodics is used for smooth muscle contraction, especially in tubular organs of the gastrointestinal tract...  in gastrointestinal hypermotility
Trihexyphenidyl Trihexyphenidyl Trihexyphenidyl , also known as benzhexol, is an antiparkinsonian agent of the antimuscarinic class. It has been in clinical usage for decades... /Benzhexol	Artane Artane Artane may refer to:* Artane, Dublin, a suburb of Dublin, Ireland.* Artane Industrial school, an Industrial school in the above suburb.* Artane, a brand-name for the drug trihexyphenidyl used to treat Parkinson's disease....	Targets the M1 Muscarinic receptor	Parkinson's disease Parkinson's disease Parkinson's disease is a degenerative disorder of the central nervous system...	Drug at relative dose has 83% activity of atropine, thus has the same side-effects
Tolterodine Tolterodine Tolterodine is an antimuscarinic drug that is used to treat urinary incontinence.It is marketed by Pfizer in Canada and the United States by its brand name Detrol. In Egypt it is also found under the trade names Tolterodine by Sabaa and Incont L.A...	Detrusitol, Detrol
Solifenacin Solifenacin Solifenacin is a urinary antispasmodic of the antimuscarinic class. It is used in the treatment of overactive bladder with or without urge incontinence. It is manufactured by Astellas and co-marketed by Astellas and GlaxoSmithKline.- Mechanism of action :Solifenacin is a competitive muscarinic...	Vesicare	Competitive muscarinic acetylcholine receptor antagonist	overactive bladder Overactive bladder Overactive bladder is a urological condition defined by a set of symptoms: urgency, with or without urge incontinence, usually with frequency and nocturia. Frequency is usually defined as urinating more than 8 times a day. The International Continence Society is responsible for this definition...  (OAB) Urgency (urge incontinence Urge incontinence Urge incontinence is a form of urinary incontinence.Urge incontinence is involuntary loss of urine occurring for no apparent reason while feeling urinary urgency, a sudden need or urge to urinate.-Causes:... )
Darifenacin Darifenacin Darifenacin is a medication used to treat urinary incontinence. It used to be marketed by Novartis; however in 2010 US rights for were sold to Warner Chilcott for 400 million US$....	Enablex	Selective for M3 receptors	Urinary incontinence	Few side effects
Benzatropine	Cogentin	Reduces the effects of the relative central cholinergic excess that occurs as a result of dopamine deficiency.	Parkinson's disease Parkinson's disease Parkinson's disease is a degenerative disorder of the central nervous system...
Mebeverine Mebeverine Mebeverine is a musculotropic antispasmodic drug without atropic side-effects whose major therapeutic role is in the treatment of irritable bowel syndrome. It is also indicated for treatment of gastrointestinal spasm secondary to organic disorder. It was first registered in 1965...	Colofac Colofac Colofac is a medicine belonging to a group of medicines known as antispasmodic agents. It usually contains 135 mg of Mebeverine Hydrochloride with the minor ingredients of lactose, potato starch, povidone, purified talc, magnesium stearate, sucrose, gelatin, acacia and carnauba wax.Colofac is... , Duspatal, Duspatalin	A muscolotropic spasmolytic with a strong and selective action on the smooth muscle spasm of the gastrointestinal tract, particularly of the colon.	Irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...  in its primary form (e.g. Abdominal Pain, Bloating, Constipation, and Diarrhea). Irritable bowel syndrome associated with organic lesions of the gastrointestinal tract. (e.g. diverticulosis & diverticulitis, etc.).	skin rashes
Procyclidine		Antimuscarinic	Drug-induced parkinsonism, akathisia and acute dystonia; Parkinson disease; and Idiopathic or secondary dystonia	Overdose produces confusion, agitation and sleeplessness that can last up to or more than 24 hours. Pupils become dilated and unreactive to light. Tachycardia (fast heart beat), as well as auditory and visual hallucinations

External links

• Effects of Muscarinic Antagonist
• Atropine (Muscarinic Receptor Antagonist), Cardiovascular Pharmacology Concepts, Richard E. Klabunde, PhD