In vivo experimental approach to treatment against tabun poisoning.
Organophosphorus compounds pose a potential threat to both military and civilian populations. Since post-exposure therapy has its limitations, our research was focused on the possibility of improving pretreatment in order to limit the toxic effects of tabun. We determined the protective index of various combinations of atropine, oximes (K074, K048, and TMB-4), and pyridostigmine given to mice before tabun intoxication. Although the tested oximes showed very good therapeutic efficacy in tabun-poisoned mice, the given pretreatments improved therapy against tabun poisoning. These regimens ensured survival of all animals up to 25.2 LD(50) of tabun. Our results indicate that even pretreatment with atropine alone is sufficiently effective in enhancing the survival of mice poisoned by multiple doses of tabun, if oxime therapy follows. K048 is our oxime of choice for future research, as it shows better protective and reactivating potency.
Berend
Suzana
S
Institute for Medical Research and Occupational Health, Ksaverska c. 2, Zagreb, Croatia. suzana@imi.hr
Katalinić
Maja
M
Vrdoljak
Ana Lucić
AL
Kovarik
Zrinka
Z
Kuca
Kamil
K
Radić
Bozica
B
D000818:Animals; D001285:Atropine / Q000494:pharmacology* / Q000627:therapeutic use; D002073:Butanes / Q000494:pharmacology / Q000627:therapeutic use; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D051379:Mice; D062025:Organophosphate Poisoning; D010755:Organophosphates; D010091:Oximes / Q000494:pharmacology* / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000494:pharmacology / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome; D014289:Trimedoxime / Q000494:pharmacology / Q000627:therapeutic use
C515196:1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide; C488676:1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane; D002073:Butanes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D010091:Oximes; D020011:Protective Agents; D011726:Pyridinium Compounds; D014289:Trimedoxime; D001285:Atropine; C009374:tabun