Pinacolyl Dimethylphosphinate (PDP) Blocks Neuromuscular Transmission; Evidence for Interaction with the Ionic Channel of the Nicotinic ACh-Receptor (A85/M/043)

摘要

Pinacolyl dimethylphosphinate (PDP) blocks neuromuscular transmission (NMT) in rat diaphragm in vitro at concentrations which, in the living animal, prevent death of soman-intoxicated animals treated with atropine and HI-6. In their blocking effects on NMT, PDP and the competitive receptor blocker gallamine, appear to have different sites of action at the nicotinic receptor. Accumulation of ACh in the synapse as a result of inhibition of endplate AChE by soman, or as a result of administration of ACh to the incubation medium, enhances the inhibiting effect of PDP on nerve impulse evoked single twitch responses, suggesting potentiation of an effect of PDP at the ionic channel sites by ACh. In addition, at low concentrations, PDP enhances twitch amplitude both at indirect and more pronounced at direct stimulation. Finally, the present results have been discussed in view of the favorable effect of PDP on survival following soman intoxication and treatment. (Copyright (c) 1987, TNO Medical Biological Laboratory.)