Acetylcholinesterase inhibitor 1584947 225024963 2008-07-11T14:53:37Z 75.27.28.150 /* Uses */ [[Image:Acetylcholine-skeletal.png|thumb|[[Acetylcholine]]]] [[Image:Acetylcholinesterase-1EA5.png|thumb|[[Acetylcholinesterase]]]] An '''acetylcholinesterase inhibitor''' or '''anti-cholinesterase''' is a [[chemical compound|chemical]] that inhibits the [[cholinesterase enzyme]] from breaking down [[acetylcholine]], so increasing both the level and duration of action of the [[neurotransmitter]] acetylcholine. == Uses == Acetylcholinesterase inhibitors: * Occur naturally as [[venom (poison)|venoms]] and [[poison]]s * Are used as weapons in the form of [[nerve agent]]s * Are used medicinally: ** To treat [[myasthenia gravis]]. In myasthenia gravis, they are used to increase neuromuscular transmission. ** To treat [[Alzheimer's disease]] ** To treat [[Lewy Body Dementia]] ** As an [[antidote]] to [[anticholinergic]] poisoning == Examples == === Reversible inhibitor === Compounds which function as [[reversible inhibitor|reversible]] [[competitive inhibitor|competitive]] or [[noncompetitive inhibitor]]s of cholinesterase are those most likely to have therapeutic uses. These include: * [[Organophosphate]]s ** [[Metrifonate]] * [[Carbamate]]s ** [[Physostigmine]] ** [[Neostigmine]] ** [[Pyridostigmine]] ** [[Ambenonium]] ** [[Demarcarium]] ** [[Rivastigmine]] * [[Phenanthrine]] derivatives ** [[Galantamine]] * [[Piperidine]]s ** [[Donepezil]], also known as ''E2020'' * [[Tacrine]], also known as tetrahydroaminoacridine (THA') * [[Edrophonium]] * [[Phenothiazines]] ==== Comparison table ==== {| class="wikitable sortable" |+ Comparison of reversible acetylcholinesterase inhibitors !Inhibitor !Duration<ref name="Rang156unless"> Unless else specified n boxes, then ref is:{{cite book |author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi=}} Page 156 </ref> !Main site of action<ref name="Rang156unless" /> !Clinical use<ref name="Rang156unless" /> !Adverse effects<ref name="Rang156unless" /> |- ! [[Edrophonium]] | short (10 min.) | [[neuromuscular junction]] | diagnosis of [[myasthenia gravis]] | |- ! [[Neostigmine]] | medium (1-2 hrs.) | [[neuromuscular junction]] | * Reverse [[neuromuscular block]] ([[intravenously]]) * Treat [[myasthenia gravis]] ([[orally]]) | visceral |- ! [[Physiostigmine]] | medium (0.5-5 hrs.) | [[postganglionic]] [[parasympathetic]] | treat [[glaucoma]] ([[eye drops]]) | |- ! [[Pyridostigmine]] | medium (2-3 hrs.) | [[neuromuscular junction]] | * Treat [[myasthenia gravis]] ([[orally]]) | |- ! [[Dyflos]] | long | [[postganglionic]] [[parasympathetic]] | historically to treat [[glaucoma]] ([[eye drops]]) | toxic |- ! [[Ecothiopate]] | long | [[postganglionic]] [[parasympathetic]] | treat [[glaucoma]] ([[eye drops]]) | [[systemic effect]]s |- ! [[Parathion]] | long | none | toxic |} === Quasi-irreversible inhibitor === Compounds which function as [[quasi-irreversible inhibitor]]s of cholinesterase are those most likely to have use as [[chemical weapon]]s or [[pesticide]]s. These include: * [[Organophosphate]]s ** [[Echothiophate]] ** [[Diisopropyl fluorophosphate]] ** [[Cyclosarin]] ** [[Dimethoate]] ** [[Sarin]] ** [[Soman]] ** [[Tabun (nerve agent)|Tabun]] ** [[VX (nerve agent)|VX]] ** [[VE (nerve agent)|VE]] ** [[VG (nerve agent)|VG]] ** [[VM (nerve agent)|VM]] ** [[Diazinon]] ** [[Malathion]] ** [[Parathion]] * [[Carbamate]]s ** [[Aldicarb]] ** [[Bendiocarb]] ** [[Bufencarb]] ** [[Carbaryl]] ** [[Carbendazim]] ** [[Carbetamide]] ** [[Carbofuran]] ** [[Chlorbufam]] ** [[Chloropropham]] ** [[Ethiofencarb]] ** [[Formetanate]] ** [[Methiocarb]] ** [[Methomyl]] ** [[Oxamyl]] ** [[Phenmedipham]] ** [[Pinmicarb]] ** [[Pirimicarb]] ** [[Propamocarb]] ** [[Propham]] ** [[Propoxur]] === Natural Compounds (Supplements) === * [[Huperzine A]] * [[Galantamine]] == Effects == Some major effects of anticholinesterases: * Actions on the autonomic nervous system, that is parasympathetic nervous system will cause bradycardia, hypotension, hypersecretion, bronchoconstriction, GI tract hypermotility, and decrease intraocular pressure. * [[SLUD]] syndrome. * Actions on the neuromuscular junction will result in prolonged muscle contraction. == See also == * [[Pesticide poisoning]] == References == <references/> == External links == * [http://www.atsdr.cdc.gov/csem/cholinesterase ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Pesticides and Chemical Warfare Nerve Agents] U.S. [[Department of Health and Human Services]] * {{MeshName|Acetylcholinesterase+inhibitors}} {{Enzyme inhibition}} {{Anticholinesterases}} {{Anti-dementia drugs}} {{Parasympathomimetics}} [[Category:Anticholinesterases|*]] [[ca:Anticolinesteràsic]] [[es:Inhibidor de la colinesterasa]] [[it:Inibitore dell'acetilcolinesterasi]] [[ja:コリンエステラーゼ阻害剤]]