Acetylcholinesterase (AChE) is a key enzyme in the nervous system that terminates neurotransmitter signaling by hydrolyzing acetylcholine (ACh). Inhibitors of AChE, whether reversible or irreversible, disrupt this process, leading to excessive ACh accumulation and overstimulation of nicotinic and muscarinic receptors, which can cause toxic effects. Reversible inhibitors, such as donepezil, rivastigmine, and galantamine, are used in the treatment of Alzheimer's disease (AD) by increasing ACh levels and improving cognitive function. These drugs are effective in managing symptoms but do not halt disease progression. Irreversible inhibitors, such as organophosphorus (OP) compounds, cause severe cholinergic toxicity by permanently inactivating AChE, leading to symptoms like muscle weakness, miosis, and respiratory failure. OPs, including insecticides and nerve agents, are highly toxic and can cause delayed neuropathy. Detoxification of OP and carbamate poisoning involves enzymatic hydrolysis, with carboxylesterases (CESs) and phosphotriesterases (PTEs) playing key roles. Oxime reactivators, such as pralidoxime, are used to reverse OP-induced AChE inhibition. Carbamates, while less toxic than OPs, are also used as pesticides and can be detoxified by CESs. The pharmacological treatment of OP poisoning includes symptomatic drugs like atropine and causal reactivators like oximes. Understanding the mechanisms of AChE inhibition and detoxification is crucial for developing effective therapies and managing poisoning.Acetylcholinesterase (AChE) is a key enzyme in the nervous system that terminates neurotransmitter signaling by hydrolyzing acetylcholine (ACh). Inhibitors of AChE, whether reversible or irreversible, disrupt this process, leading to excessive ACh accumulation and overstimulation of nicotinic and muscarinic receptors, which can cause toxic effects. Reversible inhibitors, such as donepezil, rivastigmine, and galantamine, are used in the treatment of Alzheimer's disease (AD) by increasing ACh levels and improving cognitive function. These drugs are effective in managing symptoms but do not halt disease progression. Irreversible inhibitors, such as organophosphorus (OP) compounds, cause severe cholinergic toxicity by permanently inactivating AChE, leading to symptoms like muscle weakness, miosis, and respiratory failure. OPs, including insecticides and nerve agents, are highly toxic and can cause delayed neuropathy. Detoxification of OP and carbamate poisoning involves enzymatic hydrolysis, with carboxylesterases (CESs) and phosphotriesterases (PTEs) playing key roles. Oxime reactivators, such as pralidoxime, are used to reverse OP-induced AChE inhibition. Carbamates, while less toxic than OPs, are also used as pesticides and can be detoxified by CESs. The pharmacological treatment of OP poisoning includes symptomatic drugs like atropine and causal reactivators like oximes. Understanding the mechanisms of AChE inhibition and detoxification is crucial for developing effective therapies and managing poisoning.