Mechanisms of Action of Anticholinesterases and Oximes on Acetylcholine Receptors

Oximes are strong nucleophiles, capable of activating phosphorylated acetylcholine ACh-esterase. In this report we provide evidence that, in addition to their action on the enzyme, oximes also react with nicotinic and muscarinic receptors. In our studies, we found 2-PAM, HI-6, and Toxogonin bound to both nicotinic and muscarinic ACh receptors. Modulation of binding of nicotinic receptor ligands in the Torpedo electric organ suggested that the oximes acted as nicotinic receptor antagonists. Inhibition of the receptor- regulated 22Na transport supported this conclusion. These three oximes also bound to muscarinic ACh receptors of rat brain and displaced receptor agonists e.g., 3HCD and antagonists e.g., 3HQNB and 3HPZ. Keywords Nicotinic and muscarinic acetylcholine receptors Oximes Binding of radioactive receptor ligands.