Reaktivacija fosforiliranih kolinesteraza in vitro i zaštitni učinci in vivo nekih piriridinijevih i kinolinijevih oksima

Six pyridinium and quinolinium oximes (I-VI) were tested as reactivators of serum and erythrocyte cholinesterases inhibited with 0-ethyl-S-(2-dimethylaminothioethyl)-methylphosphonate (medemo) and 0-ethyl p-nitrophenyl-ethylphosphonate (armin). They were also tested as protective agents in rats poisoned with l-methyl-2,2-dimethylpropylmethylphos-phonofluoridate (soman) and medemo. The results obtained were compared with the effect of TMB-4. Oxime IV [1.3 acetone-bis (4-pyridinium aldoxime)dichloride] proved to be a good reactivator of erythrocyte cholinesterase inhibited by medemo. Used as a protective agent together with atropine in rat poisoning it increased LD50 of medemo 48 times. Oximes I (1-benzyl-4-pyridinium aldoxime chloride) and III (l-phenacyloxime-2-pyridinium aldoxime chloride) were good reactivators of serum cholinesterase inhibited by armin and medemo. Oximes I and III used together with atropine raised LD50 in rats poisoned with medemo 20 times. Oximes III and II (l-phenacyloxime-2-pyridinium aldoxime chloride) used together with atropine increased LD50 in rats poisoned with soman 2.0 (oxime II) and 1.8 times (oxime III) respectively. Oximes V and VI (1-phenacyloxime-quinolinium chloride and 1-phenacyloxime-isoquinolinium chloride) were very toxic and did not reactivate inhibited cholinesterases at all. The effects of oximes tested were equal to or weaker than those of TMB-4 both in vitro and in viva studies.Šest piridinijevih i kinolinijevih oksima (I-VI) bili su testirani kao reaktivatori eritrocitne i serumske kolinesteraze inhibirane s 0-etil-(2-dimetilaminotioetil/-metilfosfonatom (medemo) i 0-etil-p-nitrofenil-etilfosfonatom (armin), te kao zaštitni agensi u trovanju štakora s l-metil-2,2-dimetilpropilmetilfosfonofluoridatom (soman) i medemom. Dobiveni rezultati uspoređeni su s učinkom TMB-4. Oksim IV [1,3 aceton-bis(4-piridinij-aldoksim) diklorid] pokazao se kao dobar reaktivator eritrocitne kolinesteraze inhibirane medemom, a upotrebljen zajedno s atropinom kao zaštitno sredstvo u trovanju štakora povisuje LD50 medema 48 puta. Oksim i (l-benzil-4-piridinij-aldoksim klorid) i oksim III (l-fenacil-oksim-2-piridinij-aldoksim klorid) dobro reaktiviraju serumsku kolinesterazu inhibiranu arminom i medemom. Aplicirani zajedno s atropinorn povisuju LD50 štakora otrovanih medemom 20 puta. Oksimi III i II (1-fenaciloksim-2-piridinij-aldoksim klorid) upotrebljeni zajedno s atropinom povećavaju LD50 u somana 2,0 puta (oksim II) odnosno 1,8 puta (oksim III). Oksimi V i VI (1-fenaoiloksim-kinolinij klorid i 1-fenaciloksim-isokinolinij klorid) bili su vrlo toksični i uopće nisu reaktivirali inhibirane kolinesteraze. Učinci testiranih oksima bili su jednaki ili slabiji od učinaka TMB-4 u istraživanjima in vitro i in viv