Mechanism of Interaction of Oximes with the Muscarinic Cholinergic Complex in the Central Nervous System

摘要

The present work was aimed at examining the significance of the oxime moiety and other substituents on the pyridinium rings of bisquaternary pyridinium analogs for the interactions of these drugs with rat brain muscarinic receptors. Our results indicate that TMB-4 could serve as a selective presynaptic cholinomimetic that would act synergistically with acetylcholine to block acetylcholine release. At the same time, the HGG oximes are postsynaptic allosteric antagonists, capable of increasing the ratio of antagonist to agonist binding and consequently of enhancing the blockade of muscarinic postsynaptic receptors by antagonist. It thus seems likely that a mixture of TMB-4, HGG-12 and a muscarinic antagonist would be therapeutically effective in cases of organophosphate poisoning.