Quantitative structure-activity relationships and possible mechanisms of action of bispyridinium oximes as antidotes against pinacolyl methylphosphonofluoridate.
The antidotal efficacy of bispyridinium oximes against the poisoning by pinacolyl methylphosphonofluoridate can be correlated well with their physicochemical parameters. Good correlation was observed between the efficacy of antagonism against pinacolyl methylphosphonofluoridate and antinicotinic action of these oximes. X-ray structural analysis showed that these oximes possessed structural similarity to nicotine and acetylcholine of nicotinic conformation. A new model of antidotal action, other than reactivation, against the poisoning by pinacolyl methylphosphonofluoridate was proposed for these bispyridinium oximes through nicotinic receptor binding. The antagonistic efficacy of these antidotes against pinacolyl methylphosphonofluoridate may be attributed to their direct antagonism at nicotinic receptor as well as reactivation of inhibited acetylcholinesterase.
D000818:Animals; D000931:Antidotes; D008958:Models, Molecular; D062025:Organophosphate Poisoning; D010091:Oximes / Q000627:therapeutic use*; D010261:Paraoxon / Q000506:poisoning; D011726:Pyridinium Compounds / Q000627:therapeutic use*; D051381:Rats; D012999:Soman / Q000506:poisoning*; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000931:Antidotes; D010091:Oximes; D011726:Pyridinium Compounds; D012999:Soman; D010261:Paraoxon