Interaction of Bispyridinium Oximes and Drugs Related to the Treatment of Organophosphorus Poisoning with the Mammalian Cholinergic Receptors

摘要

The exact mechanism of certain antidotes against soman and other organophosphorus (OP) nerve agents has not been fully elucidated. We have, therefore, studied the interaction of bisquaternary oximes, bispyridinium salts, muscarinic antagonists, and OP compounds with the nicotinic acetylcholine receptor (nAChR). The inhibitory effect of these drugs on the carbamylcholine-elicited increase in 22Na+ influx was examined mainly in BC3H-1 intact muscle cells. The antimuscarinic compounds aprophen and benactyzine were also examined for their affinity for the noncompetitive site of Torpedo nAChR. The following bisquaternary pyridinium compounds were studied: TMB-4, HI-6, HGG-12, HGG-42, HGG-52, HH-54, and SAD-128. The time course for the tissue distribution of various antidotes against OP poisoning was studied in mice, using tritium-labelled drugs. Concurrent use of atropine with either of these oximes for the treatment of OP poisoning may also be advantageous from the pharmacodynamic aspect. Keywords: Chemical warfare agents, Antidotes. (KT)