Postganglionic compound action potential (AP) and intracellular NAD(P)H-fluorescence were recorded simultaneously in the perifused superior cervical ganglion of the rat (SCG) to study the effects of the bispyridinium oximes HGG12, HGG42 and obidoxime.
HGG12 and HGG42 inhibit the compound action potential (AP) (IDs0:70 ~tM) and the reductive part of NAD(P)H changes (IDs0:75 ~tM) recorded upon stimulation of the SCG, while obidoxime has no ganglion blocking effects in concentrations up to 1 mM.
The effects of inhibitors of cholinergic transmission were also studied in order to understand the mechanism of action of the oximes. Hexamethonium (C6) and atropine, competitive inhibitors of receptors of nicotinic and muscarinic cholinergic transmission respectively, were found to block synaptic transmission (C6 IDs0:150 ~tM, atropine ID50:70 ~tM) and the reductive part of the NAD(P)H response (C6 IDs0 : 70 ~tM, atropine IDs0: 50 ~tM) in a quantitatively similar way.
Comparison of the ganglionic action of HGG12 and HGG42 with that of the inhibitory agents characterises them as inhibitors of receptors of nicotinic ganglionic transmission. Furthermore at concentrations of about 10 ~tM, HGG12 behaves like atropine and leads to an increase in AP and reductive fluorescence response. It is therefore probable that HGG12 has in addition an affinity for ganglionic muscarinic receptors which HGG42 does not have.