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]]