Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors.
It inhibits the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and duration of action of acetylcholine in the central nervous system, autonomic ganglia and neuromuscular junctions, which are rich in acetylcholine receptors.
Acetylcholinesterase is the primary member of the cholinesterase enzyme family.
Acetylcholinesterase inhibitors are classified as reversible, irreversible, or quasi-irreversible.
Acetylcholinesterase inhibitors (AChEIs) are a class of drugs that inhibit the enzyme acetylcholinesterase (AChE), which is responsible for the breakdown of the neurotransmitter acetylcholine (ACh).
By inhibiting AChE, these drugs increase the levels of acetylcholine in the synaptic cleft, thereby enhancing cholinergic transmission.
This mechanism is particularly beneficial in conditions like Alzheimer’s disease (AD), where there is a significant cholinergic deficit.
AChEIs used in clinical practice for the symptomatic treatment of AD include donepezil, rivastigmine, and galantamine.
These drugs provide modest improvements in cognitive function and daily living activities in patients with mild to moderate AD.
Donepezil and galantamine are reversible inhibitors, while rivastigmine is a pseudo-irreversible inhibitor.
AChEIs can modulate the cholinergic anti-inflammatory pathway, which may have implications beyond AD.
However, the use of AChEIs is often limited by gastrointestinal side effects.
Acetylcholinesterase inhibitors occur naturally as venoms and poisons and can be used as weapons in nerve agents.
They are used to treat myasthenia gravis, to increase neuromuscular transmission.
To treat glaucoma
To treat postural orthostatic tachycardia syndrome
As an antidote to anticholinergic poisoning
To reverse the effect of non-depolarizing 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, the Lewy body dementias 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.
To treat suggest efficacy in treating positive, negative and affective symptoms.
To treat autism and to increase the percentage of rapid eye movement sleep in autistic children, and encourage lucid dreaming.
Are used as insecticides (malathion)
The clinical guidelines for medication management in people with dementia recommend trialing an AChE inhibitor for people with early- to mid-stage dementia.
Potential side effects of acetylcholinesterase inhibitors.
Diarrhea Headache Insomnia Nausea Vomiting Abdominal pain Lack of appetite Yellowed skin Dizziness Slow heartbeat Sudden or substantial weight loss Weakness
Some major effects of cholinesterase inhibitors: Actions on the parasympathetic nervous system, may cause bradycardia, hypotension, hypersecretion, bronchoconstriction, GI tract hypermotility, and decrease intraocular pressure, increase lower esophageal sphincter tone.
Cholinergic crisis:
Actions on the neuromuscular junction may result in prolonged muscle contraction.
Administration of reversible cholinesterase inhibitors is contraindicated with those that have urinary retention due to urethral obstruction.
Overdose results in hyperstimulation of nicotinic and muscarinic receptors.
All cholinesterase inhibitors require doses to be increased gradually over several weeks, and this is usually referred to as the titration phase.
Compounds which function as reversible competitive or noncompetitive inhibitors of cholinesterase are those most likely to have therapeutic uses.
These include:
Carbamates Physostigmine Neostigmine Pyridostigmine Ambenonium Demecarium Rivastigmine Phenanthrene derivatives Galantamine Caffeine – noncompetitive Piperidines Donepezil Tacrine Edrophonium
Treat myasthenia gravis
Physostigmine medium (0.5–5 hrs-postganglionic parasympathetic treat glaucoma (eye drops)
Pyridostigmine medium (2–3 hrs.) neuromuscular junction Treat myasthenia gravis (orally)