Bispyridinium (oxime) compounds antagonize the "ganglion blocking" effect of pyridostigmine in isolated superior cervical ganglia of the rat.
The "antidotal effectiveness" of several bispyridinium compounds (HGG 12, HGG 65, HGG 70, HI 6, HLö and HLö 12) against the acetylcholinesterase (AChE) inhibitor pyridostigmine was evaluated in isolated superior cervical ganglia of the rat. Compound action potential amplitudes were inhibited by pyridostigmine in a concentration-dependent manner. HI 6 and atropine proved to be the most effective compounds in antagonizing the "ganglion blocking" action of pyridostigmine. Their relative effectiveness (PE value) was 5.4 and 4.2, respectively. All of the six bispyridinium compounds inhibited carbachol-induced, nicotinic, ganglionic surface depolarizations. The antinicotinic potencies of HI 6 and HLö 7 were about one order of magnitude lower (apparent KI values: 294 and 330 mumol/l) than the antinicotinic potencies of HGG 12, HGG 65, HGG 70 and HLö 12 (apparent KI values ranging from 19 to 41 mumol/l). The antinicotinic potencies of the bispyridinium compounds did not correlate with their in vitro protection of synaptic transmission in sympathetic ganglia. Moreover, the effectiveness of atropine points to the importance of antimuscarinic properties of possible "antidotes" for the maintenance of ganglionic transmission in cases of AChE poisoning.
Schlagmann
C
C
Walther Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, Federal Republic of Germany.
Ulbrich
H
H
Remien
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects*; D005730:Ganglionic Blockers / Q000037:antagonists & inhibitors*; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006801:Humans; D011726:Pyridinium Compounds / Q000494:pharmacology*; D011729:Pyridostigmine Bromide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002800:Cholinesterase Inhibitors; D005730:Ganglionic Blockers; D005731:Ganglionic Stimulants; D011726:Pyridinium Compounds; D002217:Carbachol; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide; D000109:Acetylcholine