Reactivation of Phosphorylated Acetylcholinesterase

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

Pralidoxime does not interact with carbamylated-AChE

Pralidoxime in high doses can inhibit AChE

Its quaternary ammonium group does not allow it to cross the blood brain barrier

“Aging” of phosphorylated-AChE reduces the effectiveness of pralidoxime and other oxime reactivators

Other Cholinesterase Reactivators

Diacetylmonoxime Crosses the blood brain barrier and in experimental

animals, regenerates some of the CNS cholinesterase

HI-6 is used in Europe Has two oxime centers in its structure

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

Physostigmine Neostigmine (N+) Pyridostigmine (N+) Ambenonium (N+) Demecarium (N+) Carbaryl