anticholinesterase

Anticholinesterase, or acetylcholinesterase inhibitors, are compounds that inhibit the enzyme acetylcholinesterase (AChE) or butyrylcholinesterase, thereby increasing acetylcholine levels at cholinergic synapses. They can be reversible or irreversible. By preventing hydrolysis of acetylcholine, these agents lead to its accumulation in the synaptic cleft and prolonged stimulation of both muscarinic and nicotinic receptors in the central and peripheral nervous systems.

Therapeutically, anticholinesterases have several uses. In myasthenia gravis, drugs such as pyridostigmine, neostigmine, and physostigmine improve muscle strength. In Alzheimer disease and related dementias, donepezil, rivastigmine, and galantamine aim to enhance central cholinergic transmission. Edrophonium is used diagnostically in myasthenia gravis testing. Some anticholinesterases are also used as insecticides (organophosphates like malathion) or, in high-potency forms, as chemical warfare nerve agents (sarin, VX).

Classically, inhibitors are divided into reversible and irreversible types. Reversible inhibitors (edrophonium, physostigmine, neostigmine, pyridostigmine) have shorter durations of action, whereas irreversible inhibitors, notably organophosphates, form a covalent bond with AChE and require aging to become permanently inactivated.

Adverse effects reflect excessive cholinergic activity and include bradycardia, bronchoconstriction, increased secretions, miosis, diarrhea, urination, sweating, and muscle fasciculations. In overdose, a cholinergic crisis can occur. Management focuses on atropine to counter muscarinic effects and pralidoxime (in organophosphate poisoning) to reactivate AChE, along with supportive care. Some agents vary in their selectivity for acetylcholinesterase versus butyrylcholinesterase and in their ability to cross the blood-brain barrier.