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© 1983 Oxford University Press

research-article

Quantitative Structure-Activity Relationships and Possible Mechanisms of Action of Bispyridinium Oximes as Antidotes Against Pinacolyl Methylphosphonofluoridate

CHINC-TANG SU, CHIA-PIN TANG, CHONG MA, YU-SHAN SHIH, CHONG-YEAN LIU and MOU-THAI WU

Biochemical Pharmacology Laboratory, Section of Organic Chemistry, Department of Chemistry, Chung Shan Institute of Science and Technology P.O. Box 1-4-9, Lung-Tan, Taiwan 325, Republic of China

Quantitative Structure-activity Relationships and Possible Mechanisms of Actions of Bispyridinium Oximes as Antidotes Against Pinacolyl Methylphosphonofluoridate. Su, C-T., Tang, C-P., Ma, C., Shih, Y-S-, Liu, C-Y. and Wu, M-T. (1983). Fundam. Appl. Toxicol. 3: 271–277. 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.


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