Effect of the bispyridinium oximes HGG12 and HGG42 and ganglion blocking agents on synaptic transmission and NAD(P) HFluorescence in the superior cervical ganglion of the rat after Soman poisoning in vitro

Abstract

HGG12 and HGG42 are effective therapeutic agents in experimental organophosphate poisoning even after “aging” of the phosphonylated cholinesterase ( Hauser, Kirsch, Weger, 1981). In this study we investigated their action in the isolated superior cervical ganglion of the rat (SCGR) after cholinesterase inhibition by Soman (.4 μM). As these two compounds have ganglion blocking properties (Kirsch, Weger, 1981), the action of hexamethonium bromide (C6) and atropine was also investigated and compared to theirs. The typical effects of Soman in the SCGR are a block of ganglionic transmission within 10 sec in a test train of stimuli of 6 Hz, 30 sec, and an increase of the NAD (P) H-fluorescence response up to 3 times the control value. Addition of HGG12 or HGG42 in a concentration of 30–60 μM restores transmission and decreases the metabolic response to almost normal values while obidoxime (60 μM) has no effect at all. C6 (117 μM) and to lesser degree atropine (30–60 μM) also improve ganglionic transmission and the metabolic response in cholinesterase poisoning. The pattern of amplitudes of APs in a test train of stimuli however is only restored by the HGG compounds and a comparison of equipotent concentrations (50% inhibition of AP in unpoisoned ganglia) shows that HGG12 has the best effects in Soman poisoned SCGR. The superiority of HGG12 can be explained by an inhibitory action of HGG12 on both nicotinic and muscarinic ganglionic receptors.