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The inability of standard therapy to provide adequate protection against poisoning by organophosphorus compounds (pesticides and nerve agents) motivated us to search for new, more effective oximes. We investigated the pharmacotoxicological properties of six experimental K-oximes (K027, K033, K048, K074, K075, and K203) in vivo. The therapeutic efficacy of K-oximes (at doses of 5 or 25 % of their LD^sub 50^) combined with atropine was assessed in paraoxon-poisoned mice and compared with conventionally used oximes HI-6 and TMB-4. The bisoxime K074 was the most toxic (LD^sub 50^=21.4 mg kg^sup -1^) to mice, while monoxime K027 was the least toxic (LD^sub 50^=672.8 mg kg^sup -1^). With the exception of K033, all of the tested K-oximes showed better therapeutic efficiency than HI-6 and TMB-4. K027 and K048 stood out by demonstrating low acute toxicities and ensuring protective indices ranging from 60.0 to 100.0 LD^sub 50^ of paraoxon. Taking into account that these two oximes showed a similar therapeutic efficacy regardless of the applied doses, our results suggest that K027 and K048 could be antidotes for paraoxon intoxication.
KEY WORDS: acute toxicity; mice; therapeutic efficacy
Usporedno odreðivanje ucinkovitosti bispiridinijevih oksima pri trovanju paraoksonom
Cinjenica da standardna terapija ne omogucuje dovoljnu zastitu pri otrovanju organofosfornim spojevima (pesticidima i zivcanim bojnim otrovima) potaknula nas je na istrazivanje novih, ucinkovitijih oksima. U uvjetima in vivo ispitali smo farmakotoksikoloska svojstva sest eksperimentalnih K-oksima (K027, K033, K048, K074, K075 i K203). Terapijski ucinak kombinacije K-oksima (primjenjenih u dozi 5 ili 25 % njihove LD50) i atropina testiran je na misevima otrovanim paraoksonom i usporeðen s konvencionalnim oksimima HI-6 i TMB-4. Bisoksim K074 je bio najtoksicniji (LD50=21.4 mg kg-1) za miseve, dok je monooksim K027 bio najmanje toksican (LD50=672.8 mg kg-1). Osim K033, svi K-oksimi pokazali su bolji terapijski ucinak u miseva trovanih paraoksonom u odnosu na HI-6 i TMB-4. Iz skupine testiranih oksima istaknuli su se K027 i K048 koji su pokazali nisku akutnu toksicnost i osigurali protektivne indekse u rasponu od 60.0 do 100.0 LD50 paraoksona. Uzmemo li u obzir da su ta dva oksima pokazala slican terapijski ucinak bez obzira na primjenjenu dozu, prikazani rezultati upucuju na K027 i K048 kao perspektivne antidote u terapiji trovanja paraoksonom.
KLJUCNE RIJECI: akutna toksicnost; misevi; terapijska ucinkovitost
Organophosphorus (OP) compounds are a...