Anticholinesterase, such as neostigmine, was used to be a standard drug at the end of surgery for reversal of nondepolarizing neuromuscular block. Neostigmine decreases the metabolism of acetylcholine (ACh) at the neuromuscular junction and allows its concentration to increase and overcome the effect of the muscle relaxant. But this approach is ineffective against profound block. Rapid reversal from deep block is not possible and giving a reversal agent early will not speed up the recovery time. Anticholinesterases have actions both at the nicotinic and the muscarinic receptors, and even when accompanied by an antimuscarinic agent, they produce undesirable autonomic responses. Some anticholinesterase, like donepezil, exhibits high specificity for centrally active acetylcholinesterase and raise ACh levels in the brain. The deficiency in cholinergic neurotransmission in Alzheimer's disease (AD) has led to the development of cholinesterase inhibitors as the first-line treatment for symptoms of this disease. In addition to donepezil, two other cholinesterase inhibitors have recently been approved for the treatment of AD patients. The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase. Donepezil can also reverse opioid-induced respiratory depression.
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