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|offLabelAdultNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
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<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
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<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport======Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
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|contraindications=* Condition1
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|warnings=* Description
====Precautions====
* Description
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|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
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=====Metabolic and Nutritional=====
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=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
==Overview==
The [[chemical compound]] '''acetylcholine''' (often abbreviated '''ACh''') is a [[neurotransmitter]] in both the [[peripheral nervous system]] (PNS) and [[central nervous system]] (CNS) in many organisms including [[homo sapiens|humans]]. Acetylcholine is one of many neurotransmitters in the [[autonomic nervous system]] (ANS) and the only neurotransmitter used in the [[somatic nervous system]]. It is also the neurotransmitter in all [[autonomic ganglia]].
==Chemistry==
Acetylcholine is an [[ester]] of [[acetic acid]] and [[choline]] with [[chemical formula]] [[acetyl|CH<sub><small>3</small></sub>CO]][[oxygen|O]][[methylene|CH<sub><small>2</small></sub>]][[methylene|CH<sub><small>2</small></sub>]][[Nitrogen|N]]<sup><small>+</small></sup>([[methyl|CH<sub><small>3</small></sub>]])<sub><small>3</small></sub>. This structure is reflected in the systematic name, ''2-acetoxy-N,N,N-trimethylethanaminium''.
==Function==
=====Urogenital=====
Acetylcholine has functions both in the [[peripheral nervous system]] (PNS) and in the [[central nervous system]] (CNS) as a [[neuromodulator]].
In the PNS, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system.
In the CNS, acetylcholine and the associated neurons form a [[neurotransmitter system]], the cholinergic system, which tends to cause excitatory actions.
===In PNS===
=====Miscellaneous=====
In the PNS, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system.
When acetylcholine binds to [[acetylcholine receptor]]s on [[skeletal muscle]] fibers, it opens [[ligand gated sodium channels]] in the [[cell membrane]]. Sodium ions then enter the muscle cell, stimulating muscle contraction. Acetylcholine, while inducing contraction of skeletal muscles, instead induces decreased contraction in [[cardiac muscle]] fibers. This distinction is attributed to differences in receptor structure between skeletal and cardiac fibers.
In the [[autonomic nervous system]], acetylcholine is released in the following sites:
*all pre and post-ganglionic [[parasympathetic nervous system|parasympathetic]] neurons
**preganglionic sympathetic fibers to suprarenal medulla, the modified sympathetic ganglion. On stimulation by acetylcholine, it releases [[adrenaline]] and [[noradrenaline]].
*some postganglionic sympathetic fibers : )
**sudomotor neurons to [[sweat gland]]s
===In CNS===
<!--Drug Interactions-->
In the central nervous system, ACh has a variety of effects as a [[neuromodulator]], e.g. for plasticity and excitability. Other effects are arousal and [[reward system|reward]].
|drugInteractions=* Drug
:* Description
====Structure====
<!--Use in Specific Populations-->
Acetylcholine and the associated neurons form a [[neurotransmitter system]], the cholinergic system. It originates mainly in ''pontomesencephalotegmental complex'', [[basal optic nucleus of Meynert]] and medial [[septal nucleus]], and projects axons to vast areas of the brain:
|FDAPregCat=
* The ''pontomesencephalotegmental complex'' acts mainly on [[M1 receptor]]s in the [[brainstem]] .
|useInPregnancyFDA=* '''Pregnancy Category'''
*[[basal optic nucleus of Meynert]] acts mainly on [[M1 receptor]]s in the [[neocortex]].
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
*medial [[septal nucleus]] acts mainly on [[M1 receptor]]s in the [[hippocampus]] and [[neocortex]].
====Plasticity====
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
ACh is involved with [[synaptic plasticity]], specifically in [[learning]] and [[Memory#Short-term|short-term memory]]
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
It has been shown to enhance the amplitude of synaptic potentials following [[long-term potentiation]] in many regions, including the [[dentate gyrus]], [[CA1]], [[piriform cortex]], and [[neocortex]]. This effect most likely occurs either through enhancing currents through [[NMDA]] receptors or indirectly by suppressing [[neural adaptation|adaptation]]. The suppression of adaptation has been shown in brain slices of regions CA1, [[cingulate cortex]], and piriform cortex as well as [[in vivo]] in cat [[somatosensory cortex|somatosensory]] and [[motor cortex]] by decreasing the conductance of voltage-dependent [[M current]]s and [[calcium|Ca<sup>2+</sup>]]-dependent [[potassium|K<sup>+</sup>]] currents.
<!--Administration and Monitoring-->
|administration=* Oral
====Excitability====
* Intravenous
Acetylcholine also has other effects on excitability of neurons. Its presence causes a slow [[depolarization]] by blocking a tonically active K<sup>+</sup> current, which increases neuronal excitability. Paradoxically, it increases spiking activity in [[inhibitory interneuron]]s while decreasing strength of synaptic transmission from those cells. This decrease in synaptic transmission also occurs selectively at some excitatory cells: for instance, it has an effect on intrinsic and associational fibers in layer Ib of piriform cortex, but has no effect on afferent fibers in layer Ia. Similar laminar selectivity has been shown in dentate gyrus and region CA1 of the hippocampus. One theory to explain this paradox interprets acetylcholine neuromodulation in the neocortex as modulating the estimate of expected uncertainty, acting counter to [[norepinephrine]] (NE) signals for unexpected uncertainty. Both would then decrease synaptic transition strength, but ACh would then be needed to counter the effects of NE in learning a signal understood to be noisy.
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
==Synthesis and Degradation==
* Description
Acetylcholine is synthesized in certain [[neuron]]s by the [[enzyme]] [[choline acetyltransferase]] from the compounds [[choline]] and [[acetyl-CoA]].
Normally, the enzyme [[acetylcholinesterase]] converts acetylcholine into the inactive [[metabolites]] [[choline]] and [[acetate]]. This enzyme is abundant in the synaptic cleft, and its role in rapidly clearing free acetylcholine from the synapse is essential for proper muscle function.
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
==Receptors==
<!--Overdosage-->
{{Main|Acetylcholine receptor}}
|overdose====Acute Overdose===
There are two main classes of acetylcholine receptor (AChR), [[nicotinic acetylcholine receptor]]s (nAChR) and [[muscarinic acetylcholine receptor]]s (mAChR). They are named for the [[ligands]] used to discover the receptors.
===Nicotinic===
====Signs and Symptoms====
Nicotinic AChRs are [[Ligand-gated ion channel|ionotropic receptors]] permeable to [[sodium]], [[potassium]], and [[chloride]] ions. They are stimulated by [[nicotine]] and acetylcholine. They are of two main types, muscle type and neuronal type. The former can be selectively blocked by [[curare]] and the latter by [[hexamethonium]]. The main location of nicotinic AChRs are on [[muscle]] end plates, autonomic ganglia (both sympathetic and parasympathetic), and in the CNS.<ref> Katzung, B.G. (2003). ''Basic and Clinical Pharmacology (9th ed.).'' McGraw-Hill Medical. ISBN 0-07-141092-9</ref>
===Muscarinic===
* Description
Muscarinic receptors are [[metabotropic]] and affect neurons over a longer time frame. They are stimulated by [[muscarine]] and acetylcholine, and blocked by [[atropine]]. Muscarinic receptors are found in both the central nervous system and the peripheral nervous system, in heart, lungs, upper GI tract and sweat glands. Extracts from the plant [[Deadly nightshade]] included this compound, and its action on muscarinic AChRs that increased pupil size was used for attractiveness in many European cultures in the past. Now, ACh is sometimes used during [[cataract]] surgery to produce rapid constriction of the pupil. It must be administered intraocularly because [[cornea|corneal]] [[cholinesterase]] metabolizes topically administered ACh before it can diffuse into the eye. It is sold by the trade name Miochol-E (CIBA Vision). Similar drugs are used to induce [[mydriasis]] (dilation of the pupil) in [[cardiopulmonary resuscitation]] and many other situations.
==Drugs Acting on the ACh System==
====Management====
Blocking, hindering or mimicking the action of acetylcholine has many uses in medicine. Drugs acting on the acetylcholine system are either agonists to the receptors, stimulating the system, or antagonists, inhibiting it.
=== ACh Receptor Agonists ===
* Description
Acetylcholine receptor agonists can either have an effect directly on the receptors, or exert their effects indirectly, e.g. by affecting the enzyme [[acetylcholinesterase]], which degrades the receptor ligand.
====Associated disorders====
===Chronic Overdose===
ACh Receptor Agonists are used to treat [[myasthenia gravis]] and [[Alzheimer's disease]].
=====Myasthenia gravis=====
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
The disease [[myasthenia gravis]], characterized by muscle weakness and fatigue, occurs when the body inappropriately produces [[antibody|antibodies]] against acetylcholine receptors, and thus inhibits proper acetylcholine signal transmission. Over time the motor end plate is destroyed. Drugs that competitively inhibit acetylcholinesterase (e.g., neostigmine or physostigmine) are effective in treating this disorder. They allow endogenously released acetylcholine more time to interact with its respective receptor before being inactivated by acetylcholinesterase in the gap junction.
=====Alzheimer's disease=====
<!--Pharmacology-->
Since a shortage of acetylcholine in the [[brain]] has been associated with [[Alzheimer's disease]], some drugs that inhibit acetylcholinesterase are used in the treatment of that disease. A recent study has shown that [[THC]] is one such drug, effective at reducing the formation of characteristic [[neurofibrillary tangle]]s and [[amyloid beta]] plaques<ref name="eubanks 2006">Eubanks LM, Rogers CJ, Beuscher AE 4th, Koob GF, Olson AJ, Dickerson TJ, Janda KD. "A molecular link between the active component of marijuana and Alzheimer's disease pathology." ''Molecular Pharmaceutics''. 2006 Nov-Dec; 3(6):773-7. PMID 17140265</ref>.
====Direct Acting====
<!--Drug box 2-->
* Acetylcholine
|drugBox=<!--Mechanism of Action-->
* [[Bethanechol]]
|mechAction=*
* [[Carbachol]]
* [[Cevimeline]]
* [[Pilocarpine]]
* [[Suberylcholine]]
* [[Nicotine]] (in small doses)
====Cholinesterase inhibitors====
<!--Structure-->
Most indirect acting ACh receptor agonists work by inhibiting the enzyme [[acetylcholinesterase]]. The resulting accumulation of acetylcholine causes continuous stimulation of the muscles, glands and central nervous system.
|structure=*
They are examples of [[enzyme inhibitors]], and increase the action of acetylcholine by delaying its degradation; some have been used as [[nerve agent]]s ([[Sarin]] and [[VX (nerve agent)|VX]] nerve gas) or [[pesticide]]s ([[organophosphates]] and the [[carbamates]]). Clinically they are used to reverse the action of [[muscle relaxant]]s, to treat [[myasthenia gravis]] and in [[Alzheimer's disease]] ([[rivastigmine]], which increases cholinergic activity in the brain).
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
=====Reversible=====
<!--Pharmacodynamics-->
The following substances reversibly inhibit the enzyme [[acetylcholinesterase]] (which breaks down acetylcholine), thereby increasing acetylcholine levels.
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
* Many medications in [[Alzheimer's disease]]
** [[Donepezil]]
** [[Galantamine]]
** [[Rivastigmine]]
** [[Tacrine]]
** [[THC]]
* [[Edrophonium]] (differs [[myasthenic crisis|myasthenic]] and [[cholinergic crisis]])
* [[Neostigmine]] (in [[myasthenia gravis]])
* [[Physostigmine]] (in [[glaucoma]] and [[anticholinergic]] drug overdoses)
Victims of [[sarin gas]], commonly die of suffocation as they cannot relax their [[Thoracic diaphragm|diaphragm]].
<!--Nonclinical Toxicology-->
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
====Reactivation of Acetylcholine Esterase====
<!--Clinical Studies-->
* [[Pralidoxime]]
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
=== ACh Receptor Antagonists ===
<!--How Supplied-->
====Antimuscarinic Agents====
|howSupplied=*
* [[Atropine]]
|storage=
* [[Ipratropium]]
|packLabel=
* [[Scopolamine]]
<!--Patient Counseling Information-->
* [[Tiotropium]]
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
====Ganglionic Blockers====
<!--Precautions with Alcohol-->
* [[Mecamylamine]]
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
* [[Hexamethonium]]
* [[Nicotine]] (in high doses)
* [[Trimethaphan]]
====Neuromuscular Blockers====
<!--Brand Names-->
* [[Atracurium]]
|brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
* [[Cisatracurium]]
* [[Doxacurium]]
* [[Metocurine]]
* [[Mivacurium]]
* [[Pancuronium]]
* [[Rocuronium]]
* [[Succinylcholine]]
* [[Tubocurarine]]
* [[Vecuronium]]
* [[HemiCholine]]
====Synthesis inhibitors====
<!--Look-Alike Drug Names-->
Organic [[mercurial]] compounds have a high affinity for [[thiol|sulfhydryl groups]], which causes dysfunction of the enzyme choline acetyl transferase. This inhibition may lead to acetylcholine deficiency, and can have consequences on motor function.
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
====Release inhibitors====
<!--Drug Shortage Status-->
[[Botulism toxin|Botulin]] acts by suppressing the release of acetylcholine; where the venom from a [[black widow spider]] has the reverse effect.
|drugShortage=
}}
{{PillImage
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{{LabelImage
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<!--Pill Image-->
====Other / Uncategorized / Unknown====
* [[surugatoxin]]
==History==
Acetylcholine (ACh) was first identified in 1914 by [[Henry Hallett Dale]] for its actions on heart tissue. It was confirmed as a neurotransmitter by [[Otto Loewi]] who initially gave it the name [[vagusstoff]] because it was released from the [[vagus nerve]]. Both received the 1936 [[Nobel Prize in Physiology or Medicine]] for their work.
Acetylcholine was the first [[neurotransmitter]] to be identified.
<!--Label Display Image-->
==References==
{{reflist|2}}
{{refbegin}}
*Brenner, G. M. and Stevens, C. W. (2006). ''Pharmacology (2nd ed.).'' Philadelphia, PA: W.B. Saunders Company (Elsevier). ISBN 1-4160-2984-2
*Canadian Pharmacists Association (2000). ''Compendium of Pharmaceuticals and Specialties (25th ed.)''. Toronto, ON: Webcom. ISBN 0-919115-76-4
*Carlson, NR (2001). ''Physiology of Behavior (7th ed.)''. Needham Heights, MA: Allyn and Bacon. ISBN 0-205-30840-6
*Gershon, Michael D. (1998). ''The Second Brain''. New York, NY: HarperCollins. ISBN 0-06-018252-0
*Hasselmo, ME. [http://people.bu.edu/hasselmo/HasselmoBBR1995.pdf "Neuromodulation and cortical function: Modeling the physiological basis of behavior."] ''Behavioral Brain Research''. 1995 Feb; 67(1):1-27. PMID 7748496
*Yu, AJ & [[Peter Dayan|Dayan, P]]. [http://www.gatsby.ucl.ac.uk/~dayan/papers/yud2005.pdf "Uncertainty, neuromodulation, and attention."] ''Neuron''. 2005 May 19; 46(4):681-92. PMID 15944135
{{refend}}
==External links==
* [http://www.neuro.wustl.edu/neuromuscular/mother/acetylcholine.htm Washington University (St. Louis) writeup]
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Black Box Warning
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See full prescribing information for complete Boxed Warning.
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Overview
Acetylcholine is a that is FDA approved for the of . There is a Black Box Warning for this drug as shown here. Common adverse reactions include .
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Pediatric Indications and Dosage
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Body as a Whole
Cardiovascular
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Postmarketing Experience
There is limited information regarding Postmarketing Experience of Acetylcholine in the drug label.
