An acetylcholinesterase inhibitor (often abbreviated AChEI) or anti-cholinesterase is a chemical or a drug that inhibits the acetylcholinesterase enzyme from breaking down acetylcholine, thereby increasing both the level and duration of action of the neurotransmitter acetylcholine. Acetylcholinesterase inhibitors are classified as reversible, irreversible, or quasi-irreversible (also called pseudo-irreversible).
- 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 postural tachycardia syndrome
- As an antidote to anticholinergic poisoning
- To reverse the effect of non-depolarising muscle relaxants
- To treat neuropsychiatric symptoms of diseases such as Alzheimer's disease, particularly apathy
- To increase chances of lucid dreaming (by prolonging REM sleep)
- To treat Alzheimer's disease, Lewy Body Dementia and Parkinson's disease. In these neurodegenerative conditions AChEIs are primarily used to treat the cognitive (memory and learning deficits mostly) symptoms of dementia. These symptoms are attenuated due to the role of acetylcholine in cognition in the CNS. There is some evidence to suggest that AChEIs may attenuate psychotic symptoms (especially visual hallucinations) in Parkinson's disease.
- To treat cognitive impairments in patients with schizophrenia. There is some evidence to suggest efficacy in treating positive, negative and affective symptoms.
- As a treatment for autism and to increase the percentage of Rapid eye movement sleep in autistic children, in line with the mechanism by which they encourage lucid dreaming.
|Potential side effects of acetylcholinesterase inhibitors|
|mild – usually goes away||potentially serious|
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.
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. This also prevents accidental overdose and is therefore recommended when initiating treatment with drugs that are extremely potent and/or toxic (drugs with a low therapeutic index).
- Some organophosphates not listed under "Irreversible" below
- Phenanthrene derivatives
- Caffeine – noncompetitive (also an Adenosine receptor antagonist)
- Rosmarinic acid - ester of Caffeic acid. Found in plants species of Lamiaceae family.
- Alpha-Pinene - noncompetitive reversible
- Tacrine, also known as tetrahydroaminoacridine (THA')
- Huperzine A
|Inhibitor||Duration||Main site of action||Clinical use||Adverse effects|
|Edrophonium||short (10 min.)||neuromuscular junction||diagnosis of myasthenia gravis|
|Neostigmine||medium (1–2 hrs.)||neuromuscular junction||visceral|
|Physostigmine||medium (0.5-5 hrs.)||postganglionic parasympathetic||treat glaucoma (eye drops)|
|Pyridostigmine||medium (2–3 hrs.)||neuromuscular junction|
|Dyflos||long||postganglionic parasympathetic||historically to treat glaucoma (eye drops)||toxic|
|Echothiophate (irreversible)||long||postganglionic parasympathetic||treat glaucoma (eye drops)||systemic effects|
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- Acetylcholinesterase inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH)
- Acetylcholinesterase: A gorge-ous enzyme QUite Interesting PDB Structure article at PDBe