Acetylcholinesterase inhibitor
From Wikipedia, the free encyclopedia
Not to be confused with ACE inhibitor.
An acetylcholinesterase inhibitor (often abbreviated AChEI) or anti-cholinesterase is a chemical that inhibits the acetylcholinesterase enzyme from breaking down acetylcholine, thereby increasing both the level and duration of action of the neurotransmitter acetylcholine. Reversible, quasi-irreversible (or pseudirreversible in some sources) and irreversible inhibitors exist.[1]
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Uses [edit]
Acetylcholinesterase inhibitors:
- Occur naturally as venoms and poisons
- Are used as weapons in the form of nerve agents
- Are used as insecticides
- 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
- To reverse the effect of non-depolarising muscle relaxants
Adverse effects [edit]
| Potential side effects of acetylcholinesterase inhibitors[2][3] | |||
|---|---|---|---|
| mild - usually goes away | potentially serious | ||
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Examples [edit]
Reversible inhibitor [edit]
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) [4]
- Carbamates
- Phenanthrene derivatives
- Caffeine - noncompetitive (although an Adenosine receptor antagonist)[5][6]
- Piperidines
- Donepezil, also known as E2020
- Tacrine, also known as tetrahydroaminoacridine (THA')
- Edrophonium
- Huperzine A[7][8]
- Ladostigil
- Ungeremine[9]
- Lactucopicrin
Comparison table [edit]
| Inhibitor | Duration | Main site of action | Clinical use | Adverse effects |
|---|---|---|---|---|
| Edrophonium | short (10 min.)[10] | neuromuscular junction[10] | diagnosis of myasthenia gravis[10] | |
| Neostigmine | medium (1-2 hrs.)[10] | neuromuscular junction[10] |
|
visceral[10] |
| Physostigmine | medium (0.5-5 hrs.)[10] | postganglionic parasympathetic[10] | treat glaucoma (eye drops)[10] | |
| Pyridostigmine | medium (2-3 hrs.)[10] | neuromuscular junction[10] |
|
|
| Dyflos | long[10] | postganglionic parasympathetic[10] | historically to treat glaucoma (eye drops)[10] | toxic[10] |
| Ecothiopate (irreversible) | long[10] | postganglionic parasympathetic[10] | treat glaucoma (eye drops)[10] | systemic effects[10] |
| Parathion (irreversible) | long[10] | none[10] | toxic[10] |
Quasi-irreversible inhibitor [edit]
Compounds which function as quasi-irreversible inhibitors of cholinesterase are those most likely to have use as chemical weapons or pesticides. These include:
Natural Compounds [edit]
Effects [edit]
Some major effects of cholinesterase inhibitors:
- Actions on the parasympathetic nervous system, (the parasympathetic branch of the autonomic nervous system) may 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 [edit]
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. Many other types drug treatments may require a titration or stepping up phase. This strategy is used to build tolerance to adverse events or to reach a desired clinical effect. [11]
See also [edit]
References [edit]
- ^ Pohanka, M (2012). "Acetylcholinesterase inhibitors; a patent review (2008-present)". Expert Opinion on Therapeutic Patents 22: 871–886. doi:10.1517/13543776.2012.701620. PMID 22768972.
- ^ Consumer Reports; Drug Effectiveness Review Project (May 2012). "Evaluating Prescription Drugs Used to Treat: Alzheimer’s Disease Comparing Effectiveness, Safety, and Price". Best Buy Drugs (Consumer Reports): 2. Retrieved 1 May 2013., which claims Alzheimer’s Association guidance as a source
- ^ 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.
- ^ 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.
- ^ Department of Veterinary Microbiology and Parasitology, College of Veterinary Medicine, Texas A&M University, College Station 77843-4467. http://www.ncbi.nlm.nih.gov/pubmed/2003276
- ^ Inhibition of acetylcholinesterase by caffeine, anabasine, methyl pyrrolidine and their derivatives. 1991.
- ^ Brent A. Bauer, M.D. Alzheimer's disease http://www.mayoclinic.com/health/huperzine-a/AN02022
- ^ Wang, BS; Wang, H; Wei, ZH; Song, YY; Zhang, L; Chen, HZ (2009). "Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis.". Journal of neural transmission (Vienna, Austria : 1996) 116 (4): 457–65. doi:10.1007/s00702-009-0189-x. PMID 19221692.
- ^ 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.
- ^ 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 [edit]
- ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Insecticides and Chemical Warfare Nerve Agents U.S. Department of Health and Human Services
- Acetylcholinesterase inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH)
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