1. 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

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

3. Oxime Phosphonate and Regenerated AChE3

4. 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

5. 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

6. Edrophonium

7. Edrophonium is a Short Acting Inhibitor that Binds to the Ionic Site but Not to the Esteratic Site of AChE

8. Acetylcholinesterase Inhibition

9. Inhibition of Acetylcholinesterase Produces Stimulation of All Cholinergic Sites9

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