New bispyridinium oximes: in vitro and in vivo evaluation of their biological efficiency in soman and tabun poisoning.
Improving the efficacy of antidotal treatment of poisonings with nerve agents is still a challenge for the scientific community. This study investigated the interactions of four bispyridinium oximes with human erythrocyte acetylcholinesterase (AChE) and their effects on soman- and tabun-poisoned mice. Oximes HI-6 and TMB-4 were used for comparison. These oximes inhibited AchE with inhibitory potency (IC(50)) ranging from 0.02 to 1.0 mM. The best reactivating potency (%R) was obtained with K074, when AChE was inhibited by tabun. The protective potency (P(50)) of all oximes in human erythrocyte AChE inhibited by soman and tabun could not be determined. In tabun-poisoned mice very good antidotal efficacy was obtained with K027, K048, and K074, which makes them interesting for future investigation. The combination of HI-6 and atropine is the therapy of choice for soman poisoning.
Institute for Medical Research and Occupational Health, Ksaverska c. 2, Zagreb, Croatia. suzana@imi.hr
Suzana
S
Berend
Ana Lucić
AL
Vrdoljak
Bozica
B
Radić
Kamil
K
Kuca
D000818:Animals; D002619:Chemical Warfare Agents / Q000506:poisoning*; D004793:Enzyme Reactivators / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D062025:Organophosphate Poisoning; D010755:Organophosphates; D010091:Oximes / Q000494:pharmacology* / Q000627:therapeutic use; D011041:Poisoning / Q000188:drug therapy; D011726:Pyridinium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D012999:Soman / Q000506:poisoning*
D002619:Chemical Warfare Agents; D004793:Enzyme Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D012999:Soman; C009374:tabun