Reactivation of Phosphorylated Acetylcholinesterase
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Oximes are used to reactivate phosphorylated AChE
The group (=NOH) has a high affinity for the phosphorus atom
Pralidoxime has a nucleophilic site that interacts with the
phosphorylated site on phosphorylated-AChE
Pralidoxime Reacts Chemically with Phosphorylated-AChE
The oxime group makes a nucleophilic attack upon the phosphorus atom
Oxime Phosphonate and Regenerated AChE
Limitations of Pralidoxime
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Pralidoxime does not interact with carbamylatedAChE
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Pralidoxime in high doses can inhibit AChE
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Its quaternary ammonium group does not allow it to
cross the blood brain barrier
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“Aging” of phosphorylated-AChE reduces the
effectiveness of pralidoxime and other oxime
reactivators
Other Cholinesterase Reactivators
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Diacetylmonoxime
 Crosses the blood brain barrier and in experimental
animals, regenerates some of the CNS cholinesterase
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HI-6 is used in Europe
 Has two oxime centers in its structure
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More potent than pralidoxime
Edrophonium
Edrophonium is a Short Acting Inhibitor that Binds
to the Ionic Site but Not to the Esteratic Site of AChE
Acetylcholinesterase Inhibition
Inhibition of Acetylcholinesterase Produces
Stimulation of All Cholinergic Sites
Carbamyl Inhibitors of AChE
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Physostigmine
Neostigmine (N+)
Pyridostigmine (N+)
Ambenonium (N+)
Demecarium (N+)
Carbaryl