Acetylcholinesterase inhibitor

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An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the cholinesterase enzyme from breaking down acetylcholine, so increasing both the level and duration of action of the neurotransmitter acetylcholine.

Contents 1 Uses 2 Examples 2.1 Reversible inhibitor 2.1.1 Comparison table 2.2 Quasi-irreversible inhibitor 2.3 Natural Compounds (Supplements) 3 Effects 4 See also 5 References 6 External links

[edit] Uses

Acetylcholinesterase inhibitors:

• Occur naturally as venoms and poisons
• Are used as weapons in the form of nerve agents
• Are used medicinally:
  • To treat myasthenia gravis. In myasthenia gravis, they are used to increase neuromuscular transmission.
  • To treat Alzheimer's disease
  • As an antidote to anticholinergic poisoning

[edit] Examples

[edit] Reversible inhibitor

Compounds which function as reversible competitive or noncompetitive inhibitors of cholinesterase are those most likely to have therapeutic uses. These include:

• Organophosphates
  • Metrifonate
• Carbamates
  • Physostigmine
  • Neostigmine
  • Pyridostigmine
  • Ambenonium
  • Demarcarium
  • Rivastigmine
• Phenanthrine derivatives
  • Galantamine
• Piperidines
  • Donepezil, also known as E2020
• Tacrine, also known as tetrahydroaminoacridine (THA')
• Edrophonium
• Phenothiazines

[edit] Comparison table

Comparison of reversible acetylcholinesterase inhibitors

Inhibitor	Duration[1]	Main site of action[1]	Clinical use[1]	Adverse effects[1]
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 effects
Parathion	long	none	toxic

[edit] Quasi-irreversible inhibitor

Compounds which function as quasi-irreversible inhibitors of cholinesterase are those most likely to have use as chemical weapons or pesticides. These include:

• Organophosphates
  • Echothiophate
  • Diisopropyl fluorophosphate
  • Cyclosarin
  • Dimethoate
  • Sarin
  • Soman
  • Tabun
  • VX
  • VE
  • VG
  • VM
  • Diazinon
  • Malathion
  • Parathion
• Carbamates
  • Aldicarb
  • Bendiocarb
  • Bufencarb
  • Carbaryl
  • Carbendazim
  • Carbetamide
  • Carbofuran
  • Chlorbufam
  • Chloropropham
  • Ethiofencarb
  • Formetanate
  • Methiocarb
  • Methomyl
  • Oxamyl
  • Phenmedipham
  • Pinmicarb
  • Pirimicarb
  • Propamocarb
  • Propham
  • Propoxur

[edit] Natural Compounds (Supplements)

• Huperzine A
• Galantamine

[edit] 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.

[edit] See also

• Pesticide poisoning

[edit] References

1. ^ ^{a b c d} Unless else specified n boxes, then ref is:Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.  Page 156

[edit] External links

• ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Pesticides and Chemical Warfare Nerve Agents U.S. Department of Health and Human Services
• MeSH Acetylcholinesterase+inhibitors

v • d • e Pharmacology: enzyme inhibition Class Competitive inhibition - Uncompetitive inhibition - Non-competitive inhibition - Suicide inhibition - Mixed inhibition Substrate Oxidoreductase (EC 1): Aromatase inhibitors - Lipoxygenase inhibitor - Monoamine oxidase inhibitors Transferase (EC 2): Integrase inhibitor - Kinase inhibitors - Reverse transcriptase inhibitors Hydrolase (EC 3): Acetylcholinesterase inhibitors - Phosphodiesterase inhibitors - Protease inhibitors (ACE inhibitor, Trypsin inhibitor) Lyase (EC 4): Carbonic anhydrase inhibitors

v • d • e Anticholinesterases (N06DA, N07AA) Carbamates Ambenonium - Demecarium - Stigmine (Neostigmine, Physostigmine, Pyridostigmine, Rivastigmine) Other Galantamine - Metrifonate - Donepezil - Tacrine - Edrophonium

v • d • e Psychoanaleptics: anti-dementia drugs (N06D) Anticholinesterases Tacrine - Donepezil - Rivastigmine - Galantamine Other NMDA receptor antagonist (Memantine) - Ginkgo biloba

v • d • e Parasympathomimetics (N07A) Anticholinesterases Stigmine (Neostigmine, Pyridostigmine, Distigmine) - Ambenonium Choline esters Carbachol - Bethanechol Other parasympathomimetics Pilocarpine - Choline alfoscerate