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 1

Pralidoxime Reacts Chemically with Phosphorylated-AChE The oxime group makes a nucleophilic attack upon the phosphorus atom 2

Oxime Phosphonate and Regenerated AChE 3

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 4

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 5

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 9

Carbamyl Inhibitors of AChE Physostigmine Neostigmine (N+) Pyridostigmine (N+) Ambenonium (N+) Demecarium (N+) Carbaryl 10