esteraseinhibitors

Esterase inhibitors are chemicals that reduce the activity of esterases, a group of enzymes that hydrolyze ester bonds in a wide range of substrates, including neurotransmitters, drugs, and environmental chemicals. They can be broadly classified as reversible inhibitors and irreversible inhibitors, often acting on acetylcholinesterase (AChE) and related enzymes such as butyrylcholinesterase (BuChE).

Reversible esterase inhibitors bind non-covalently and dissociate over time. Examples include edrophonium, physostigmine, neostigmine, and pyridostigmine, as well as several drugs used to treat neurological disorders. Donepezil, rivastigmine, and galantamine are AChE inhibitors approved for symptomatic treatment of Alzheimer's disease. These agents increase acetylcholine levels at cholinergic synapses and have established clinical roles in MG and dementia, among other indications.

Irreversible inhibitors form strong covalent bonds with esterases, leading to long-lasting inactivation. This category includes organophosphates (such as parathion, malathion, and certain nerve agents like sarin) and some carbamates. Organophosphates phosphorylate the active-site serine and can undergo aging, creating a barrier to rapid reactivation. Carbamates temporarily carbamylate the enzyme but are typically more readily reversible than organophosphates.

Applications and safety: Esterase inhibitors have important medical uses in neuromuscular and neurodegenerative diseases but carry the risk of cholinergic toxicity if overdosed. Treatment of poisoning may involve atropine to block muscarinic effects and pralidoxime (2-PAM) to reactivate AChE after organophosphate exposure, along with supportive care.