Acetylcholinesterase inhibitor
Oxford A-Z of Medicinal Drugs:
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acetylcholinesterase inhibitors
A class of drugs that inhibit the action of acetylcholinesterase, an enzyme that breaks down the neurotransmitter acetylcholine. They therefore increase the amount of acetylcholine that is available for the transmission of nerve impulses. The acetylcholinesterase inhibitors donepezil hydrochloride, galantamine, and rivastigmine exert their effects in the brain. They are used in the treatment of Alzheimer's disease, which is associated with a loss in the activity of acetylcholine-secreting nerve cells in the brain.
| acetylcholine chloride, acetylcholine, acetic acid | |
| acetylcysteine, aciclovir, acid-peptic diseases |
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Acetylcholinesterase inhibitor
Not to be confused with ACE inhibitor.
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.
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Contents
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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 Glaucoma
- To treat Alzheimer's disease
- To treat Lewy Body Dementia
- To treat Postural Tachycardia Syndrome
- As an antidote to anticholinergic poisoning
Examples
Reversible inhibitor
Compounds which function as reversible competitive or noncompetitive inhibitors of cholinesterase are those most likely to have therapeutic uses. These include:
- Some organophosphates not listed under "Irreversible" below
- Delta9-tetrahydrocannabinol (THC) [1]
- Carbamates
- Physostigmine
- Neostigmine
- Pyridostigmine
- Ambenonium
- Demarcarium
- Rivastigmine
- Phenanthrene derivatives
- Caffeine - noncompetitive (although an Adenosine receptor antagonist)
- Piperidines
- Donepezil, also known as E2020
- Tacrine, also known as tetrahydroaminoacridine (THA')
- Edrophonium
- Huperzine A
- Ladostigil
- Ungeremine[2]
- Lactucopicrin
Comparison table
| Inhibitor | Duration | Main site of action | Clinical use | Adverse effects |
|---|---|---|---|---|
| Edrophonium | short (10 min.)[3] | neuromuscular junction[3] | diagnosis of myasthenia gravis[3] | |
| Neostigmine | medium (1-2 hrs.)[3] | neuromuscular junction[3] |
|
visceral[3] |
| Physostigmine | medium (0.5-5 hrs.)[3] | postganglionic parasympathetic[3] | treat glaucoma (eye drops)[3] | |
| Pyridostigmine | medium (2-3 hrs.)[3] | neuromuscular junction[3] |
|
|
| Dyflos | long[3] | postganglionic parasympathetic[3] | historically to treat glaucoma (eye drops)[3] | toxic[3] |
| Ecothiopate | long[3] | postganglionic parasympathetic[3] | treat glaucoma (eye drops)[3] | systemic effects[3] |
| Parathion (irreversible) | long[3] | none[3] | toxic[3] |
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:
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Natural Compounds
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.
Administration of reversible cholinoesterase inhibitors is contraindicated with those that have urinary retention due to obstruction.
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.[4]
See also
References
- ^ Eubanks LM, Rogers CJ, Beuscher AE, et al. (2006). "A molecular link between the active component of marijuana and Alzheimer's disease pathology". Mol. Pharm. 3 (6): 773–7. doi:10.1021/mp060066m. PMC 2562334. PMID 17140265. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2562334.
- ^ Rhee IK, I; Appels N, Hofte B, Karabatak B, Erkelens C, Stark LM, Flippin LA, Verpoorte R (November 2004). "Isolation of the Acetylcholinesterase Inhibitor Ungeremine from Nerine bowdenii by Preparative HPLC Coupled On-Line to a Flow Assay System". Biological & Pharmaceutical Bulletin 27 (11): 1804–1809. PMID 15516727. http://www.jstage.jst.go.jp/article/bpb/27/11/1804/_pdf.
- ^ a b c d e f g h i j k l m n o p q r s t u v w x y Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 156
- ^ Inglis, F (2002). "The tolerability and safety of cholinesterase inhibitors in the treatment of dementia.". International journal of clinical practice. Supplement (127): 45–63. PMID 12139367.
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
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