An acetylcholinesterase inhibitor (often abbreviated AChEI) or anti-cholinesterase is a chemical that inhibits the cholinesterase enzyme from breaking down acetylcholine, 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 3 Effects 4 Titration phase 5 See also 6 References 7 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
  • To treat Lewy Body Dementia
  • 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 (irreversible)
• Carbamates
  • Physostigmine
  • Neostigmine
  • Pyridostigmine
  • Ambenonium
  • Demarcarium
  • Rivastigmine
• Phenanthrene derivatives
  • Galantamine
• Piperidines
  • Donepezil, also known as E2020
• Tacrine, also known as tetrahydroaminoacridine (THA')
• Edrophonium
• Huperzine A

[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
Physostigmine	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 (irreversible)	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:

[edit] Natural Compounds

• Huperzine A
• Galantamine
• Onchidal

[edit] Effects

Some major effects of cholinesterase inhibitors:

• Actions on the autonomic nervous system, that is parasympathetic nervous system will cause bradycardia, hypotension, hypersecretion, bronchoconstriction, GI tract hypermotility, and decrease intraocular pressure.
• SLUDGE syndrome.
• Actions on the neuromuscular junction will result in prolonged muscle contraction.

[edit] Titration phase

When used in the central nervous system to alleviate neurological symptoms, such as rivastigmine in Alzheimer's disease, all cholinesterase inhibitors require doses to be increased gradually over several weeks, and this is usually referred to as the titration phase.^[2]

[edit] See also

• Pesticide poisoning

[edit] References

[edit] External links

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

v • d • e Pharmacology: enzyme inhibition Class Competitive inhibition · Uncompetitive inhibition · Non-competitive inhibition · Suicide inhibition · Mixed inhibition Substrate Oxidoreductase (EC 1) Aromatase · Lipoxygenase · Monoamine oxidase · COX-2 · Xanthine oxidase · Dihydrofolate reductase · Ribonucleotide reductase · 5-alpha-reductase Transferase (EC 2) Integrase · Protein kinase · Reverse transcriptase · COMT · Thymidylate synthase · Dihydropteroate synthetase · Farnesyltransferase · GABA transaminase Hydrolase (EC 3) Acetylcholinesterase · Phosphodiesterase · Protease (ACE, Trypsin) · Histone deacetylase · Dipeptidyl peptidase-4 Lyase (EC 4) Carbonic anhydrase · Dopa decarboxylase

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

v • d • e Parasympathomimetics / cholinergic agonists / acetylcholinesterase inhibitors (N06DA, N07AA) Direct (at receptor) muscarinic: Muscarine  · Oxotremorine  · M1 (Vedaclidine • Xanomeline)  · M3 (Bethanechol, Pilocarpine, Arecoline, Cevimeline, Aceclidine)  · Methacholine nicotinic: Nicotine (low doses) · Lobeline · Varenicline · Epibatidine  · Dimethylphenylpiperazinium M & N: Acetylcholine/Choline alfoscerate · Carbachol Indirect/AIs (in synapse) Reversible very short acting: Edrophonium carbamates/stigmine: Ambenonium · Rivastigmine · Distigmine · tertiary/CNS (Physostigmine) · quaternary/peripheral (Neostigmine, Pyridostigmine) anti-dementia (Galantamine, Donepezil, Tacrine) Irreversible/ organophosphate ophthalmological (Ecothiopate, Isoflurophate, Demecarium) antiparasitic (Malathion, Metrifonate) chemical warfare (see Nerve agent)

v • d • e Neuromodulation Types Enzyme: Inducer • Inhibitor Ion Channel: Opener • Blocker Receptor: Agonist • Antagonist • Positive Allosteric Modulator (PAM) • Negative Allosteric Modulator (NAM) Transporter [Reuptake]: Enhancer (RE) • Inhibitor (RI) • Releaser (RA) Miscellaneous: Precursor • Cofactor Classes Enzyme (refer to Enzyme Inhibitors for more details) Ion Channel Calcium Channel Blocker (CCB) • Potassium Channel Blocker (PCB) • Sodium Channel Blocker (SCB) • Potassium Channel Opener (PCO) Receptor & Transporter Adrenergic Adrenergic Receptor Agonist (α, β (1, 2)) • Adrenergic Receptor Antagonist (α (1, 2), β) • Adrenergic Reuptake Inhibitor (ARI) Cholinergic Acetylcholine Receptor Agonist (Muscarinic, Nicotinic) • Acetylcholine Receptor Antagonist (Muscarinic, Nicotinic (Ganglionic, Muscular)) Dopaminergic Dopamine Receptor Agonist • Dopamine Receptor Antagonist • Dopamine Reuptake Inhibitor (DRI) Endocannabinoid Cannabinoid Receptor Agonist • Cannabinoid Receptor Antagonist Histaminergic Histamine Receptor Agonist • Histamine Receptor Antagonist (H1, H2, H3) GABAergic GABA Receptor Agonist • GABA Receptor Antagonist • GABA Reuptake Inhibitor (GRI) Glutamatergic Glutamate Receptor Agonist (AMPA) • Glutamate Receptor Antagonist (NMDA) Opioid Opioid Receptor Agonist • Opioid Receptor Antagonist Serotonergic Serotonin Receptor Agonist (5-HT4) • Serotonin Receptor Antagonist (5-HT3) • Serotonin Reuptake Inhibitor (SRI) • Serotonin Reuptake Enhancer (SRE) Other Adenosine Reuptake Inhibitor (AdoRI) • Angiotensin Receptor Antagonist • Endothelin Receptor Antagonist • NK1 Receptor Antagonist • Vasopressin Receptor Antagonist Miscellaneous Cofactor (see Enzyme Cofactors) • Precursor (see Amino Acids)