Competitive Binding of the Oximes HI-6 and 2-PAM with Regional Brain Muscarinic Receptors

摘要

Because of their ability to reactivate acetylcholinesterase in the peripheral nervous system, the oximes HI-6 and 2-PAM are used to treat organophosphorous poisoning. Thecentral effects of these compounds may derive from their ability to interact with muscarinic cholinerrgicc receptors. Neutral membranes were isolated from hippocampus, striatum and cortex, and the effects of HI-6 and 2-PAM on muscarinic receptor binding were assessed in a competitive binding assay using 3H-QNB as the binding ligand. Both oximes were able to displace 3H-QNB from the receptor with 2-PAM being about four times as potent as HI-6. The binding shows regional specificity and occurs at physiologically relevant concentrations, suggesting that these oximes directly effect central cholinergic receptors.