Stojiljković, Miloš P.

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  • Stojiljković, Miloš P. (11)
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Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos

Antonijević, Biljana; Stojiljković, Miloš P.; Bokonjić, Dubravko; Vučinić, Slavica

(Vojnomedicinska akademija - Institut za naučne informacije, Beograd, 2011)

TY  - JOUR
AU  - Antonijević, Biljana
AU  - Stojiljković, Miloš P.
AU  - Bokonjić, Dubravko
AU  - Vučinić, Slavica
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1602
AB  - Introduction/Aim. In acute organophosphate poisoning the issue of special concern is the appearance of muscle fasciculations and convulsions that cannot be adequately antagonised by the use of atropine and oxime therapy. The aim of this study was to examine atidotal effect of obidoxime or HI-6 combinations with memantine in mice poisoned with soman, dichlorvos or heptenophos. Methods. Male Albino mice were pretreated intravenously (iv) with increasing doses of oximes and/or memantine (10 mg/kg) at various times before poisoning with 1.3 LD-50 of soman, dichlorvos or heptenophos, in order to determine the median effective dose and the efficacy half-time. In a separate experiment, cerebral extravasation of Evans blue dye (40 mg/kg iv) was examined after application of memantine (10 mg/kg iv), midazolam (2.5 mg/kg intraperitonealy - ip) and ketamine (20 mg/kg ip) 5 minutes before soman (1 LD-50 subcutaneously - sc). Results. Coadministration of memantine induced a significant decrease in median effective dose in null time of both HI-6 (7.96 vs 1.79 mmoL/kg in soman poisoning) and obidoxime (16.80 vs 2.75 mmoL/kg in dichlorvos poisoning; 21.56 vs 6.63 mmoL/kg in heptenophos poisoning). Memantine and midazolam succeeded to counteract the soman-induced proconvulsive activity. Conclusion. Memantine potentiated the antidotal effect of HI-6 against a lethal dose of soman, as well as the ability of obidoxime to antagonize the toxic effects of dichlorvos and heptenophos probably partly due to its anticonvulsive properties.
AB  - Uvod/Cilj. Poseban problem pri trovanju organofosfornim jedinjenjima predstavljaju mišićne fascikulacije i konvulzije, koje se ne mogu u potpunosti antagonizovati primenom atropina i oksima. Cilj ovog rada bio je ispitivanje antidotskog efekta kombinacije memantina i oksima HI-6 kod trovanja somanom, kao i kombinacije memantina sa obidoksimom kod trovanja dihlorvosom i heptenofosom. Metode. Albino miševima, mužjacima, u repnu venu date su rastuće doze oksima i/ili memantina (10 mg/kg) u različitim vremenskim intervalima pre intravenskog (iv) davanja 1,3 LD-50 somana, dihlorvosa ili heptenofosa. Praćenjem stepena preživljanja, izračunate su srednje efektivne doze i poluvreme efikasnosti. U odvojenom eksperimentu praćena je cerebralna ekstravazacija boje Evans plavo (40 mg/kg iv) nakon primene memantina (10 mg/kg iv), midazolama (2,5 mg/kg intraoperitonealno - ip) i ketamina (20 mg/kg ip) 5 min pre davanja somana (1 LD-50 supkutano - sc). Rezultati. Primenom kombinacija sa memantinom srednje efektivne doze u nultom vremenu i HI-6 (7,96 vs 1,79 mmoL/kg kod trovanja somanom) i obidoksima (16,80 vs 2,75 mmoL/kg kod trovanja dihlorvosom; 21,56 vs 6,63 mmoL/kg kod trovanja heptenofosom) bile su višestruko niže u odnosu na dozu samog oksima. Memantin i midazolam uspešno su suprimirali prokonvulzivni efekat somana. Zaključak. Rezultati ove studije pokazuju da primena memantina u kombinaciji sa oksimima obezbeđuje bolji zaštitni efekat nego sam oksim, a u osnovi ovog efekta verovatno leži i njegov antikonvulzivni potencijal.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos
T1  - Antidotski efekat kombinacija obidoksim/HI-6 i memantina kod miševa trovanih somanom, dihlorvosom ili heptenofosom
VL  - 68
IS  - 12
SP  - 1033
EP  - 1040
DO  - 10.2298/VSP1112033A
ER  - 
@article{
author = "Antonijević, Biljana and Stojiljković, Miloš P. and Bokonjić, Dubravko and Vučinić, Slavica",
year = "2011",
abstract = "Introduction/Aim. In acute organophosphate poisoning the issue of special concern is the appearance of muscle fasciculations and convulsions that cannot be adequately antagonised by the use of atropine and oxime therapy. The aim of this study was to examine atidotal effect of obidoxime or HI-6 combinations with memantine in mice poisoned with soman, dichlorvos or heptenophos. Methods. Male Albino mice were pretreated intravenously (iv) with increasing doses of oximes and/or memantine (10 mg/kg) at various times before poisoning with 1.3 LD-50 of soman, dichlorvos or heptenophos, in order to determine the median effective dose and the efficacy half-time. In a separate experiment, cerebral extravasation of Evans blue dye (40 mg/kg iv) was examined after application of memantine (10 mg/kg iv), midazolam (2.5 mg/kg intraperitonealy - ip) and ketamine (20 mg/kg ip) 5 minutes before soman (1 LD-50 subcutaneously - sc). Results. Coadministration of memantine induced a significant decrease in median effective dose in null time of both HI-6 (7.96 vs 1.79 mmoL/kg in soman poisoning) and obidoxime (16.80 vs 2.75 mmoL/kg in dichlorvos poisoning; 21.56 vs 6.63 mmoL/kg in heptenophos poisoning). Memantine and midazolam succeeded to counteract the soman-induced proconvulsive activity. Conclusion. Memantine potentiated the antidotal effect of HI-6 against a lethal dose of soman, as well as the ability of obidoxime to antagonize the toxic effects of dichlorvos and heptenophos probably partly due to its anticonvulsive properties., Uvod/Cilj. Poseban problem pri trovanju organofosfornim jedinjenjima predstavljaju mišićne fascikulacije i konvulzije, koje se ne mogu u potpunosti antagonizovati primenom atropina i oksima. Cilj ovog rada bio je ispitivanje antidotskog efekta kombinacije memantina i oksima HI-6 kod trovanja somanom, kao i kombinacije memantina sa obidoksimom kod trovanja dihlorvosom i heptenofosom. Metode. Albino miševima, mužjacima, u repnu venu date su rastuće doze oksima i/ili memantina (10 mg/kg) u različitim vremenskim intervalima pre intravenskog (iv) davanja 1,3 LD-50 somana, dihlorvosa ili heptenofosa. Praćenjem stepena preživljanja, izračunate su srednje efektivne doze i poluvreme efikasnosti. U odvojenom eksperimentu praćena je cerebralna ekstravazacija boje Evans plavo (40 mg/kg iv) nakon primene memantina (10 mg/kg iv), midazolama (2,5 mg/kg intraoperitonealno - ip) i ketamina (20 mg/kg ip) 5 min pre davanja somana (1 LD-50 supkutano - sc). Rezultati. Primenom kombinacija sa memantinom srednje efektivne doze u nultom vremenu i HI-6 (7,96 vs 1,79 mmoL/kg kod trovanja somanom) i obidoksima (16,80 vs 2,75 mmoL/kg kod trovanja dihlorvosom; 21,56 vs 6,63 mmoL/kg kod trovanja heptenofosom) bile su višestruko niže u odnosu na dozu samog oksima. Memantin i midazolam uspešno su suprimirali prokonvulzivni efekat somana. Zaključak. Rezultati ove studije pokazuju da primena memantina u kombinaciji sa oksimima obezbeđuje bolji zaštitni efekat nego sam oksim, a u osnovi ovog efekta verovatno leži i njegov antikonvulzivni potencijal.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos, Antidotski efekat kombinacija obidoksim/HI-6 i memantina kod miševa trovanih somanom, dihlorvosom ili heptenofosom",
volume = "68",
number = "12",
pages = "1033-1040",
doi = "10.2298/VSP1112033A"
}
Antonijević, B., Stojiljković, M. P., Bokonjić, D.,& Vučinić, S.. (2011). Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 68(12), 1033-1040.
https://doi.org/10.2298/VSP1112033A
Antonijević B, Stojiljković MP, Bokonjić D, Vučinić S. Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos. in Vojnosanitetski pregled. 2011;68(12):1033-1040.
doi:10.2298/VSP1112033A .
Antonijević, Biljana, Stojiljković, Miloš P., Bokonjić, Dubravko, Vučinić, Slavica, "Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos" in Vojnosanitetski pregled, 68, no. 12 (2011):1033-1040,
https://doi.org/10.2298/VSP1112033A . .
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Unequal efficacy of pyridinium oximes in acute organophosphate poisoning

Antonijević, Biljana; Stojiljković, Miloš P.

(2007)

TY  - JOUR
AU  - Antonijević, Biljana
AU  - Stojiljković, Miloš P.
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/994
AB  - The use of organophosphorus pesticides results in toxicity risk to non-target organisms. Organophosphorus compounds share a common mode of action, exerting their toxic effects primarily via acetylcholinesterase (AChE) inhibition. Consequently, acetylcholine accumulates in the synaptic clefts of muscles and nerves, leading to overstimulation of cholinergic receptors. Acute cholinergic crisis immediately follows exposure to organophosphate and includes signs and symptoms resulting from hyperstimulation of central and peripheral muscarinic and nicotinic receptors. The current view of the treatment of organophosphate poisoning includes three strategies, i.e. the use of an anticholinergic drug (e.g., atropine), cholinesterase-reactivating agents (e.g., oximes) and anticonvulsant drugs (e.g., benzodiazepines). Oximes, as a part of antidotal therapy, ensure the recovery of phosphylated enzymes via a process denoted as reactivation of inhibited AChE. However, both experimental results and clinical findings have demonstrated that different oximes are not equally effective against poisonings caused by structurally different organophosphorus compounds. Therefore, antidotal characteristics of conventionally used oximes can be evaluated regarding how close the certain substance is to the theoretical concept of the universal oxime. Pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LüH-6), HI-6 and HLö-7 have all been demonstrated to be very effective in experimental poisonings with sarin and VX.TMEM and LüH-6 may reactivate tabun-inhibited AChE, whereas HI-6 possesses the ability to reactivate the soman-inhibited enzyme. An oxime HLö-7 seems to be an efficient reactivator of AChE inhibited by any of the four organophosphorus warfare agents. According to the available literature, the oximes LüH-6 and TMB-4, although relatively toxic, are the most potent to induce reactivation of AChE inhibited by the majority of organophosphorus pesticides. Since there are no reports of controlled clinical trials on the use of TMB-4 in human organophosphate pesticide poisoning, LüH-6 may be a better option.
T2  - Clinical Medicine and Research
T1  - Unequal efficacy of pyridinium oximes in acute organophosphate poisoning
VL  - 5
IS  - 1
SP  - 71
EP  - 82
DO  - 10.3121/cmr.2007.701
ER  - 
@article{
author = "Antonijević, Biljana and Stojiljković, Miloš P.",
year = "2007",
abstract = "The use of organophosphorus pesticides results in toxicity risk to non-target organisms. Organophosphorus compounds share a common mode of action, exerting their toxic effects primarily via acetylcholinesterase (AChE) inhibition. Consequently, acetylcholine accumulates in the synaptic clefts of muscles and nerves, leading to overstimulation of cholinergic receptors. Acute cholinergic crisis immediately follows exposure to organophosphate and includes signs and symptoms resulting from hyperstimulation of central and peripheral muscarinic and nicotinic receptors. The current view of the treatment of organophosphate poisoning includes three strategies, i.e. the use of an anticholinergic drug (e.g., atropine), cholinesterase-reactivating agents (e.g., oximes) and anticonvulsant drugs (e.g., benzodiazepines). Oximes, as a part of antidotal therapy, ensure the recovery of phosphylated enzymes via a process denoted as reactivation of inhibited AChE. However, both experimental results and clinical findings have demonstrated that different oximes are not equally effective against poisonings caused by structurally different organophosphorus compounds. Therefore, antidotal characteristics of conventionally used oximes can be evaluated regarding how close the certain substance is to the theoretical concept of the universal oxime. Pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LüH-6), HI-6 and HLö-7 have all been demonstrated to be very effective in experimental poisonings with sarin and VX.TMEM and LüH-6 may reactivate tabun-inhibited AChE, whereas HI-6 possesses the ability to reactivate the soman-inhibited enzyme. An oxime HLö-7 seems to be an efficient reactivator of AChE inhibited by any of the four organophosphorus warfare agents. According to the available literature, the oximes LüH-6 and TMB-4, although relatively toxic, are the most potent to induce reactivation of AChE inhibited by the majority of organophosphorus pesticides. Since there are no reports of controlled clinical trials on the use of TMB-4 in human organophosphate pesticide poisoning, LüH-6 may be a better option.",
journal = "Clinical Medicine and Research",
title = "Unequal efficacy of pyridinium oximes in acute organophosphate poisoning",
volume = "5",
number = "1",
pages = "71-82",
doi = "10.3121/cmr.2007.701"
}
Antonijević, B.,& Stojiljković, M. P.. (2007). Unequal efficacy of pyridinium oximes in acute organophosphate poisoning. in Clinical Medicine and Research, 5(1), 71-82.
https://doi.org/10.3121/cmr.2007.701
Antonijević B, Stojiljković MP. Unequal efficacy of pyridinium oximes in acute organophosphate poisoning. in Clinical Medicine and Research. 2007;5(1):71-82.
doi:10.3121/cmr.2007.701 .
Antonijević, Biljana, Stojiljković, Miloš P., "Unequal efficacy of pyridinium oximes in acute organophosphate poisoning" in Clinical Medicine and Research, 5, no. 1 (2007):71-82,
https://doi.org/10.3121/cmr.2007.701 . .
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206

Application of modeling for evaluation of the efficacy of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats

Stefanović, D.; Antonijević, Biljana; Bokonjić, Dubravko; Milovanović, Zoran A.; Stojiljković, Miloš P.; Nedeljković, M.

(Savez farmaceutskih udruženja Srbije, Beograd, 2006)

TY  - CONF
AU  - Stefanović, D.
AU  - Antonijević, Biljana
AU  - Bokonjić, Dubravko
AU  - Milovanović, Zoran A.
AU  - Stojiljković, Miloš P.
AU  - Nedeljković, M.
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/866
PB  - Savez farmaceutskih udruženja Srbije, Beograd
C3  - Arhiv za farmaciju
T1  - Application of modeling for evaluation of the efficacy of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats
T1  - Primena modela pri evaluaciji efikasnosti trimedoksima, atropina i natrijum-hidrogenkarbonata kod trovanja dihlorvosom u pacova
VL  - 56
IS  - 4
SP  - 602
EP  - 603
UR  - https://hdl.handle.net/21.15107/rcub_farfar_866
ER  - 
@conference{
author = "Stefanović, D. and Antonijević, Biljana and Bokonjić, Dubravko and Milovanović, Zoran A. and Stojiljković, Miloš P. and Nedeljković, M.",
year = "2006",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Application of modeling for evaluation of the efficacy of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats, Primena modela pri evaluaciji efikasnosti trimedoksima, atropina i natrijum-hidrogenkarbonata kod trovanja dihlorvosom u pacova",
volume = "56",
number = "4",
pages = "602-603",
url = "https://hdl.handle.net/21.15107/rcub_farfar_866"
}
Stefanović, D., Antonijević, B., Bokonjić, D., Milovanović, Z. A., Stojiljković, M. P.,& Nedeljković, M.. (2006). Application of modeling for evaluation of the efficacy of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 56(4), 602-603.
https://hdl.handle.net/21.15107/rcub_farfar_866
Stefanović D, Antonijević B, Bokonjić D, Milovanović ZA, Stojiljković MP, Nedeljković M. Application of modeling for evaluation of the efficacy of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats. in Arhiv za farmaciju. 2006;56(4):602-603.
https://hdl.handle.net/21.15107/rcub_farfar_866 .
Stefanović, D., Antonijević, Biljana, Bokonjić, Dubravko, Milovanović, Zoran A., Stojiljković, Miloš P., Nedeljković, M., "Application of modeling for evaluation of the efficacy of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats" in Arhiv za farmaciju, 56, no. 4 (2006):602-603,
https://hdl.handle.net/21.15107/rcub_farfar_866 .

Response surface modeling in evaluation of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats

Stefanović, D.; Antonijević, Biljana; Bokonjić, Dubravko; Milovanović, Zoran A.; Stojiljković, Miloš P.; Nedeljković, Mirjana

(Elsevier, 2006)

TY  - CONF
AU  - Stefanović, D.
AU  - Antonijević, Biljana
AU  - Bokonjić, Dubravko
AU  - Milovanović, Zoran A.
AU  - Stojiljković, Miloš P.
AU  - Nedeljković, Mirjana
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/711
PB  - Elsevier
C3  - Toxicology Letters
T1  - Response surface modeling in evaluation of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats
VL  - 164, Supplement
SP  - S244
EP  - S244
DO  - 10.1016/j.toxlet.2006.07.167
ER  - 
@conference{
author = "Stefanović, D. and Antonijević, Biljana and Bokonjić, Dubravko and Milovanović, Zoran A. and Stojiljković, Miloš P. and Nedeljković, Mirjana",
year = "2006",
publisher = "Elsevier",
journal = "Toxicology Letters",
title = "Response surface modeling in evaluation of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats",
volume = "164, Supplement",
pages = "S244-S244",
doi = "10.1016/j.toxlet.2006.07.167"
}
Stefanović, D., Antonijević, B., Bokonjić, D., Milovanović, Z. A., Stojiljković, M. P.,& Nedeljković, M.. (2006). Response surface modeling in evaluation of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats. in Toxicology Letters
Elsevier., 164, Supplement, S244-S244.
https://doi.org/10.1016/j.toxlet.2006.07.167
Stefanović D, Antonijević B, Bokonjić D, Milovanović ZA, Stojiljković MP, Nedeljković M. Response surface modeling in evaluation of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats. in Toxicology Letters. 2006;164, Supplement:S244-S244.
doi:10.1016/j.toxlet.2006.07.167 .
Stefanović, D., Antonijević, Biljana, Bokonjić, Dubravko, Milovanović, Zoran A., Stojiljković, Miloš P., Nedeljković, Mirjana, "Response surface modeling in evaluation of trimedoxime, atropine and sodium bicarbonate against dichlorvos poisoning in rats" in Toxicology Letters, 164, Supplement (2006):S244-S244,
https://doi.org/10.1016/j.toxlet.2006.07.167 . .

Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos

Stefanović, D; Antonijević, Biljana; Bokonjić, Dubravko; Stojiljković, Miloš P.; Milovanović, Zoran A.; Nedeljković, M

(Wiley, Hoboken, 2006)

TY  - JOUR
AU  - Stefanović, D
AU  - Antonijević, Biljana
AU  - Bokonjić, Dubravko
AU  - Stojiljković, Miloš P.
AU  - Milovanović, Zoran A.
AU  - Nedeljković, M
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/773
AB  - The development of effective antidotes against organophosphates such as dichlorvos has been a persistent challenge over the past decades. Therapy of organophosphate poisoning is based on the administration of atropine and oxime as standard antidotes. The present study was undertaken to evaluate the ability of sodium bicarbonate to improve protective effects of standard antidotes in rats poisoned with dichlorvos. The aim of this experiment was to establish the correlation between protective effects and biochemical parameters relevant for acid-base status. In order to examine the protective effect of both standard antidotes and their combinations, groups of experimental animals were poisoned subcutaneously with increasing doses of dichlorvos. Immediately thereafter, rats were treated with atropine 10 mg/kg intramuscularly, oximes 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally. These antidotes were administered either as single doses or in combinations. In the biochemical part of the experiments, rats were poisoned with dichlorvos 1.3 LD50 (10.64 mg/kg) subcutaneously and immediately thereafter treated with atropine 10 mg/kg intramuscularly, oximes (trimedoxime or obidoxime) 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally either as single doses or in combinations. Parameters relevant for acid-base status were measured 10 minutes after the administration of antidotes. The results of our study indicate that addition of sodium bicarbonate to standard antidotes significantly improves protective effects of atropine, obidoxime and trimedoxime. Correlation between protection and biochemical outcome is clearly evident when sodium bicarbonate is being added to atropine.
PB  - Wiley, Hoboken
T2  - Basic & Clinical Pharmacology & Toxicology
T1  - Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos
VL  - 98
IS  - 2
SP  - 173
EP  - 180
DO  - 10.1111/j.1742-7843.2006.pto_68.x
ER  - 
@article{
author = "Stefanović, D and Antonijević, Biljana and Bokonjić, Dubravko and Stojiljković, Miloš P. and Milovanović, Zoran A. and Nedeljković, M",
year = "2006",
abstract = "The development of effective antidotes against organophosphates such as dichlorvos has been a persistent challenge over the past decades. Therapy of organophosphate poisoning is based on the administration of atropine and oxime as standard antidotes. The present study was undertaken to evaluate the ability of sodium bicarbonate to improve protective effects of standard antidotes in rats poisoned with dichlorvos. The aim of this experiment was to establish the correlation between protective effects and biochemical parameters relevant for acid-base status. In order to examine the protective effect of both standard antidotes and their combinations, groups of experimental animals were poisoned subcutaneously with increasing doses of dichlorvos. Immediately thereafter, rats were treated with atropine 10 mg/kg intramuscularly, oximes 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally. These antidotes were administered either as single doses or in combinations. In the biochemical part of the experiments, rats were poisoned with dichlorvos 1.3 LD50 (10.64 mg/kg) subcutaneously and immediately thereafter treated with atropine 10 mg/kg intramuscularly, oximes (trimedoxime or obidoxime) 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally either as single doses or in combinations. Parameters relevant for acid-base status were measured 10 minutes after the administration of antidotes. The results of our study indicate that addition of sodium bicarbonate to standard antidotes significantly improves protective effects of atropine, obidoxime and trimedoxime. Correlation between protection and biochemical outcome is clearly evident when sodium bicarbonate is being added to atropine.",
publisher = "Wiley, Hoboken",
journal = "Basic & Clinical Pharmacology & Toxicology",
title = "Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos",
volume = "98",
number = "2",
pages = "173-180",
doi = "10.1111/j.1742-7843.2006.pto_68.x"
}
Stefanović, D., Antonijević, B., Bokonjić, D., Stojiljković, M. P., Milovanović, Z. A.,& Nedeljković, M.. (2006). Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos. in Basic & Clinical Pharmacology & Toxicology
Wiley, Hoboken., 98(2), 173-180.
https://doi.org/10.1111/j.1742-7843.2006.pto_68.x
Stefanović D, Antonijević B, Bokonjić D, Stojiljković MP, Milovanović ZA, Nedeljković M. Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos. in Basic & Clinical Pharmacology & Toxicology. 2006;98(2):173-180.
doi:10.1111/j.1742-7843.2006.pto_68.x .
Stefanović, D, Antonijević, Biljana, Bokonjić, Dubravko, Stojiljković, Miloš P., Milovanović, Zoran A., Nedeljković, M, "Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos" in Basic & Clinical Pharmacology & Toxicology, 98, no. 2 (2006):173-180,
https://doi.org/10.1111/j.1742-7843.2006.pto_68.x . .
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24

Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos

Antonijević, Biljana; Bokonjić, Dubravko; Stojiljković, Miloš P.; Kilibarda, Vesna; Milovanović, Zoran A.; Nedeljković, M; Maksimović, M

(Wiley, Hoboken, 2005)

TY  - JOUR
AU  - Antonijević, Biljana
AU  - Bokonjić, Dubravko
AU  - Stojiljković, Miloš P.
AU  - Kilibarda, Vesna
AU  - Milovanović, Zoran A.
AU  - Nedeljković, M
AU  - Maksimović, M
PY  - 2005
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/632
AB  - The aim of the study was to examine antidotal potency of trimedoxime in mice poisoned with three direct dimethoxy-substituted organophosphorus inhibitors. In order to assess the protective efficacy of trimedoxime against dichlorvos, heptenophos or monocrotophos, median effective doses and efficacy half-times were calculated. Trimedoxime (24 mg/kg intravenously) was injected 5 min. before 1.3 LD50 intravenously of poisons. Activities of brain, diaphragmal and erythrocyte acetylcholinesterase, as well as of plasma carboxylesterases were determined at different time intervals (10, 40 and 60 min.) after administration of the antidotes. Protective effect of trimedoxime decreased according to the following order: monocrotophos > heptenophos > dichlorvos. Administration of the oxime produced a significant reactivation of central and peripheral acetylcholinesterase inhibited with dichlorvos and heptenophos, with the exception of erythrocyte acetylcholinesterase inhibited by heptenophos. Surprisingly, trimedoxime did not induce reactivation of monocrotophos-inhibited acetylcholinesterase in any of the tissues tested. These organophosphorus compounds produced a significant inhibition of plasma carboxylesterase activity, while administration of trimedoxime led to regeneration of the enzyme activity. The same dose of trimedoxime assured survival of experimental animals poisoned by all three organophosphorus compounds, although the biochemical findings were quite different.
PB  - Wiley, Hoboken
T2  - Basic & Clinical Pharmacology & Toxicology
T1  - Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos
VL  - 96
IS  - 2
SP  - 111
EP  - 117
DO  - 10.1111/j.1742-7843.2005.pto960204.x
ER  - 
@article{
author = "Antonijević, Biljana and Bokonjić, Dubravko and Stojiljković, Miloš P. and Kilibarda, Vesna and Milovanović, Zoran A. and Nedeljković, M and Maksimović, M",
year = "2005",
abstract = "The aim of the study was to examine antidotal potency of trimedoxime in mice poisoned with three direct dimethoxy-substituted organophosphorus inhibitors. In order to assess the protective efficacy of trimedoxime against dichlorvos, heptenophos or monocrotophos, median effective doses and efficacy half-times were calculated. Trimedoxime (24 mg/kg intravenously) was injected 5 min. before 1.3 LD50 intravenously of poisons. Activities of brain, diaphragmal and erythrocyte acetylcholinesterase, as well as of plasma carboxylesterases were determined at different time intervals (10, 40 and 60 min.) after administration of the antidotes. Protective effect of trimedoxime decreased according to the following order: monocrotophos > heptenophos > dichlorvos. Administration of the oxime produced a significant reactivation of central and peripheral acetylcholinesterase inhibited with dichlorvos and heptenophos, with the exception of erythrocyte acetylcholinesterase inhibited by heptenophos. Surprisingly, trimedoxime did not induce reactivation of monocrotophos-inhibited acetylcholinesterase in any of the tissues tested. These organophosphorus compounds produced a significant inhibition of plasma carboxylesterase activity, while administration of trimedoxime led to regeneration of the enzyme activity. The same dose of trimedoxime assured survival of experimental animals poisoned by all three organophosphorus compounds, although the biochemical findings were quite different.",
publisher = "Wiley, Hoboken",
journal = "Basic & Clinical Pharmacology & Toxicology",
title = "Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos",
volume = "96",
number = "2",
pages = "111-117",
doi = "10.1111/j.1742-7843.2005.pto960204.x"
}
Antonijević, B., Bokonjić, D., Stojiljković, M. P., Kilibarda, V., Milovanović, Z. A., Nedeljković, M.,& Maksimović, M.. (2005). Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos. in Basic & Clinical Pharmacology & Toxicology
Wiley, Hoboken., 96(2), 111-117.
https://doi.org/10.1111/j.1742-7843.2005.pto960204.x
Antonijević B, Bokonjić D, Stojiljković MP, Kilibarda V, Milovanović ZA, Nedeljković M, Maksimović M. Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos. in Basic & Clinical Pharmacology & Toxicology. 2005;96(2):111-117.
doi:10.1111/j.1742-7843.2005.pto960204.x .
Antonijević, Biljana, Bokonjić, Dubravko, Stojiljković, Miloš P., Kilibarda, Vesna, Milovanović, Zoran A., Nedeljković, M, Maksimović, M, "Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos" in Basic & Clinical Pharmacology & Toxicology, 96, no. 2 (2005):111-117,
https://doi.org/10.1111/j.1742-7843.2005.pto960204.x . .
9
10
10

Influence of sodium bicarbonate and standard antidotes on acid-base status in rats poisoned with dichlorvos

Stefanović, Danka; Antonijević, Biljana; Bokonjić, Dubravko; Stojiljković, Miloš P.; Milovanović, Zoran A.; Nedeljković, Mirjana

(Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd, 2004)

TY  - JOUR
AU  - Stefanović, Danka
AU  - Antonijević, Biljana
AU  - Bokonjić, Dubravko
AU  - Stojiljković, Miloš P.
AU  - Milovanović, Zoran A.
AU  - Nedeljković, Mirjana
PY  - 2004
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/565
AB  - The aim of the present work was to examine potential beneficial role of sodium bicarbonate (3 mmol/kg ip) on protective potency of trimedoxime (10 mg/kg im), obidoxime (10 mg/kg im) and atropine (10 mg/kg im) in rats poisoned with dichlorvos. Special attention was paid to the influence of co-administration of sodium bicarbonate on acid-base status in experimental animals poisoned with dichlorvos (1.3 LD50 sc). Coadministration of sodium bicarbonate significantly increased protective effect of standard antidotes in rats poisoned with dichlorvos. Sodium bicarbonate given along with atropine/oxime produced an increase in blood pH value and correction of acidosis. In conclusion, correlation between protective effect and biochemical outcome was evident when sodium bicarbonate was added to antidotes.
AB  - Cilj rada je bio da se ispita efekat natrijum bikarbonata (3 mmol/kg ip) na zaštitni potencijal trimedoksima (10 mg/kg im), obidoksima (10 mg/kg im) i atropina (10 mg/kg im) u pacova trovanih dihlorvosom. Posebna pažnja je posvećena uticaju kombinacija natrijum bikarbonata i antidota na acido-bazni status eksperimentalnih životinja trovanih dihlorvosom (1.3 LD50 ). Primena kombinacija sa natrijum bikarbonatom zna- čajno je povećala zaštitne efekte standardnih antidota, a došlo je i do porasta vrednosti pH krvi i korekcije acidoze. Takođe, moglo se zaključiti da kada je natrijum bikarbonat dat zajedno sa atropinom/oksimom postoji jasna korelacija između dobijenih zaštitnih efekata i testiranih biohemijskih parametara.
PB  - Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd
T2  - Jugoslovenska medicinska biohemija
T1  - Influence of sodium bicarbonate and standard antidotes on acid-base status in rats poisoned with dichlorvos
T1  - Uticaj natrijum bikarbonata i standardnih antidota na acido-bazni status pacova trovanih dihlorvosom
VL  - 23
IS  - 2
SP  - 165
EP  - 170
DO  - 10.2298/JMH0402165S
ER  - 
@article{
author = "Stefanović, Danka and Antonijević, Biljana and Bokonjić, Dubravko and Stojiljković, Miloš P. and Milovanović, Zoran A. and Nedeljković, Mirjana",
year = "2004",
abstract = "The aim of the present work was to examine potential beneficial role of sodium bicarbonate (3 mmol/kg ip) on protective potency of trimedoxime (10 mg/kg im), obidoxime (10 mg/kg im) and atropine (10 mg/kg im) in rats poisoned with dichlorvos. Special attention was paid to the influence of co-administration of sodium bicarbonate on acid-base status in experimental animals poisoned with dichlorvos (1.3 LD50 sc). Coadministration of sodium bicarbonate significantly increased protective effect of standard antidotes in rats poisoned with dichlorvos. Sodium bicarbonate given along with atropine/oxime produced an increase in blood pH value and correction of acidosis. In conclusion, correlation between protective effect and biochemical outcome was evident when sodium bicarbonate was added to antidotes., Cilj rada je bio da se ispita efekat natrijum bikarbonata (3 mmol/kg ip) na zaštitni potencijal trimedoksima (10 mg/kg im), obidoksima (10 mg/kg im) i atropina (10 mg/kg im) u pacova trovanih dihlorvosom. Posebna pažnja je posvećena uticaju kombinacija natrijum bikarbonata i antidota na acido-bazni status eksperimentalnih životinja trovanih dihlorvosom (1.3 LD50 ). Primena kombinacija sa natrijum bikarbonatom zna- čajno je povećala zaštitne efekte standardnih antidota, a došlo je i do porasta vrednosti pH krvi i korekcije acidoze. Takođe, moglo se zaključiti da kada je natrijum bikarbonat dat zajedno sa atropinom/oksimom postoji jasna korelacija između dobijenih zaštitnih efekata i testiranih biohemijskih parametara.",
publisher = "Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd",
journal = "Jugoslovenska medicinska biohemija",
title = "Influence of sodium bicarbonate and standard antidotes on acid-base status in rats poisoned with dichlorvos, Uticaj natrijum bikarbonata i standardnih antidota na acido-bazni status pacova trovanih dihlorvosom",
volume = "23",
number = "2",
pages = "165-170",
doi = "10.2298/JMH0402165S"
}
Stefanović, D., Antonijević, B., Bokonjić, D., Stojiljković, M. P., Milovanović, Z. A.,& Nedeljković, M.. (2004). Influence of sodium bicarbonate and standard antidotes on acid-base status in rats poisoned with dichlorvos. in Jugoslovenska medicinska biohemija
Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd., 23(2), 165-170.
https://doi.org/10.2298/JMH0402165S
Stefanović D, Antonijević B, Bokonjić D, Stojiljković MP, Milovanović ZA, Nedeljković M. Influence of sodium bicarbonate and standard antidotes on acid-base status in rats poisoned with dichlorvos. in Jugoslovenska medicinska biohemija. 2004;23(2):165-170.
doi:10.2298/JMH0402165S .
Stefanović, Danka, Antonijević, Biljana, Bokonjić, Dubravko, Stojiljković, Miloš P., Milovanović, Zoran A., Nedeljković, Mirjana, "Influence of sodium bicarbonate and standard antidotes on acid-base status in rats poisoned with dichlorvos" in Jugoslovenska medicinska biohemija, 23, no. 2 (2004):165-170,
https://doi.org/10.2298/JMH0402165S . .
3
3

Protective effect of standard antidotes along with sodium bicarbonate in rats poisoned with dichlorvos

Antonijević, Biljana; Stefanović, Danka; Nedeljković, Mirjana; Stojiljković, Miloš P.; Bokonjić, Dubravko; Milovanović, Zoran A.

(Savez farmaceutskih udruženja Srbije, Beograd, 2002)

TY  - CONF
AU  - Antonijević, Biljana
AU  - Stefanović, Danka
AU  - Nedeljković, Mirjana
AU  - Stojiljković, Miloš P.
AU  - Bokonjić, Dubravko
AU  - Milovanović, Zoran A.
PY  - 2002
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/368
PB  - Savez farmaceutskih udruženja Srbije, Beograd
C3  - Arhiv za farmaciju
T1  - Protective effect of standard antidotes along with sodium bicarbonate in rats poisoned with dichlorvos
T1  - Zaštitni efekat standardnih antidota primenjenih sa natrijum bikarbonatom u pacova trovanih dihlorvosom
VL  - 52
IS  - 4
SP  - 762
EP  - 763
UR  - https://hdl.handle.net/21.15107/rcub_farfar_368
ER  - 
@conference{
author = "Antonijević, Biljana and Stefanović, Danka and Nedeljković, Mirjana and Stojiljković, Miloš P. and Bokonjić, Dubravko and Milovanović, Zoran A.",
year = "2002",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Protective effect of standard antidotes along with sodium bicarbonate in rats poisoned with dichlorvos, Zaštitni efekat standardnih antidota primenjenih sa natrijum bikarbonatom u pacova trovanih dihlorvosom",
volume = "52",
number = "4",
pages = "762-763",
url = "https://hdl.handle.net/21.15107/rcub_farfar_368"
}
Antonijević, B., Stefanović, D., Nedeljković, M., Stojiljković, M. P., Bokonjić, D.,& Milovanović, Z. A.. (2002). Protective effect of standard antidotes along with sodium bicarbonate in rats poisoned with dichlorvos. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 52(4), 762-763.
https://hdl.handle.net/21.15107/rcub_farfar_368
Antonijević B, Stefanović D, Nedeljković M, Stojiljković MP, Bokonjić D, Milovanović ZA. Protective effect of standard antidotes along with sodium bicarbonate in rats poisoned with dichlorvos. in Arhiv za farmaciju. 2002;52(4):762-763.
https://hdl.handle.net/21.15107/rcub_farfar_368 .
Antonijević, Biljana, Stefanović, Danka, Nedeljković, Mirjana, Stojiljković, Miloš P., Bokonjić, Dubravko, Milovanović, Zoran A., "Protective effect of standard antidotes along with sodium bicarbonate in rats poisoned with dichlorvos" in Arhiv za farmaciju, 52, no. 4 (2002):762-763,
https://hdl.handle.net/21.15107/rcub_farfar_368 .

Potential beneficial action of adamantanes in mice poisoned with soman

Antonijević, Biljana; Maksimović, Matej; Kilibarda, Vesna; Stojiljković, Miloš P.; Nedeljković, Mirjana; Milovanović, Zoran A.; Bokonjić, Dubravko

(Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd, 2001)

TY  - JOUR
AU  - Antonijević, Biljana
AU  - Maksimović, Matej
AU  - Kilibarda, Vesna
AU  - Stojiljković, Miloš P.
AU  - Nedeljković, Mirjana
AU  - Milovanović, Zoran A.
AU  - Bokonjić, Dubravko
PY  - 2001
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/305
AB  - The aim of this study was to investigate the efficacy of four pyridinium oximes - pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LuH-6) and HI-6 - alone or in combination with memantine and its principal metabolite 1-amino-3-hydroxymethyl-5-methyl adamantane (Mrz 2/373) against soman in mice. Male Albino mice were pretreated iv with oximes and adamantanes at various times before 1.3 LD-50 of soman iv in order to obtain their ED-50t. In a separate experiment, the brain, dia­phragmai and erythrocytic acetylcholinesterase and plasma carboxylesterase activities were determined after sacrificing mice 5 min after soman 0.75 LD-50. Oxime HI-6 (ED-50 value at 5 min before soman) and adamantanes were administered 5 min before soman. In the combination regimens and in the biochemical experiments the dose of memantine and Mrz 2/373 was fixed at 10 mg/kg iv. Along the tested time intervals, HI-6 afforded the best protection of experimental animals, and calculated EDSOo value of HI-6 was 7.96 µmol/kg. Memantine significantly (up to 9 times) de­creased ED-500 values of all the oximes used, with the exception of TMB-4. Among tested tis­sues, the highest recovery of inhibited acetylcholinesterase was obtained in the diaphragm. Co-administration of adamantanes (memantine, Mrz 2/373) produced a statistically significant in­crease in the erythrocyte acetylcholinesterase activity. It could be concluded that memantine antidotal efficacy could be ascribed to the protection of acetylcholinesterase activity. .
AB  - Pored činjenice daje oksim HI-6 najefikasniji u antagonizovanju toksičnih efekata somana, terapija trovanja ovim nervnim bojnim otrovom još nije u potpunosti zadovoljavajuća. Dosadašnji eksperimenti sa memantinom su pokazali da ovaj derivat adamantana potencira terapijski efekat standardnih antidota pri trovanju organofosfornim jedinjenjima. U ovom radu ispitivana je antidotska efikasnost piridinijumskih oksima - pralidoksima, trimedoksima, obidoksima i HI-6, kao i njihovih kombinacija sa memantinom ili njegovim aktivnim metabolitom Mrz 2/373 u miševa trovanih somanom. Radi dobijanja parametara zaštitne efikasnosti antidota, albino miševima mužjacima su iv aplikovane rastuće doze antidota u određenim vremenskim intervalima ( 1 -60 min) pre 1,3 LD-50 iv somana. Aktivnosti acetilholinesteraze mozga, dijafragme i eritrocita, kao i karboksilesteraza plazme, određivane su nakon iv primene adamantana (10 mg/kg) i/ili oksima HI-6 (3,1 mg/kg; 7,96 µmol/kg) datih 5 min pre 0,75 LD-50 iv somana. Primena oksima HI-6 je obezbedila najbolju zaštitu eksperimentalnih životinja, a srednja efektivna doza u nultom vremenu ED-500 iznosila je 7,96 µmol/kg. Kada je primenjen u kombinaciji sa oksimima, memantin je doveo do značajnog (oko 9 puta) smanjenja HD-500 vrednosti svih oksima, osim trimedoksima. ali je zato poluvreme efikasnosti trimedoksima povećano 4,82 puta. Značajan porast acetilholinesteraze dijafragme dobijen je primenom HI-6, memantina kao i njihove kombinacije. U odnosu na grupu koja je primila samo soman, aktivnost acetilholi­nesteraze eritrocita bila je značajno veća u grupama kojima su davani adamantani i/ili HI-6. Nijedan od primenjenih tretmana nije doveo do statistički značajnog povećanja aktivnosti acetilholinesteraze mozga i karboksilesteraza plazme. Bolji zaštitni efekt kombinacija oksima i memantina u odnosu na same oksime mogao bi se pripisati antikonvulzivnom potencijalu memantina, koji je nekompetitivni antagonista NMDA receptora, ali i izvesnoj zaštiti aktivnog centra acetilholinesteraze dijafragme.
PB  - Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd
T2  - Archives of Toxicology, Kinetics and Xenobiotic Metabolism
T1  - Potential beneficial action of adamantanes in mice poisoned with soman
T1  - Potencijalna uloga adamantana u trovanju miševa somanom
VL  - 9
IS  - 1-2
SP  - 13
EP  - 20
UR  - https://hdl.handle.net/21.15107/rcub_farfar_305
ER  - 
@article{
author = "Antonijević, Biljana and Maksimović, Matej and Kilibarda, Vesna and Stojiljković, Miloš P. and Nedeljković, Mirjana and Milovanović, Zoran A. and Bokonjić, Dubravko",
year = "2001",
abstract = "The aim of this study was to investigate the efficacy of four pyridinium oximes - pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LuH-6) and HI-6 - alone or in combination with memantine and its principal metabolite 1-amino-3-hydroxymethyl-5-methyl adamantane (Mrz 2/373) against soman in mice. Male Albino mice were pretreated iv with oximes and adamantanes at various times before 1.3 LD-50 of soman iv in order to obtain their ED-50t. In a separate experiment, the brain, dia­phragmai and erythrocytic acetylcholinesterase and plasma carboxylesterase activities were determined after sacrificing mice 5 min after soman 0.75 LD-50. Oxime HI-6 (ED-50 value at 5 min before soman) and adamantanes were administered 5 min before soman. In the combination regimens and in the biochemical experiments the dose of memantine and Mrz 2/373 was fixed at 10 mg/kg iv. Along the tested time intervals, HI-6 afforded the best protection of experimental animals, and calculated EDSOo value of HI-6 was 7.96 µmol/kg. Memantine significantly (up to 9 times) de­creased ED-500 values of all the oximes used, with the exception of TMB-4. Among tested tis­sues, the highest recovery of inhibited acetylcholinesterase was obtained in the diaphragm. Co-administration of adamantanes (memantine, Mrz 2/373) produced a statistically significant in­crease in the erythrocyte acetylcholinesterase activity. It could be concluded that memantine antidotal efficacy could be ascribed to the protection of acetylcholinesterase activity. ., Pored činjenice daje oksim HI-6 najefikasniji u antagonizovanju toksičnih efekata somana, terapija trovanja ovim nervnim bojnim otrovom još nije u potpunosti zadovoljavajuća. Dosadašnji eksperimenti sa memantinom su pokazali da ovaj derivat adamantana potencira terapijski efekat standardnih antidota pri trovanju organofosfornim jedinjenjima. U ovom radu ispitivana je antidotska efikasnost piridinijumskih oksima - pralidoksima, trimedoksima, obidoksima i HI-6, kao i njihovih kombinacija sa memantinom ili njegovim aktivnim metabolitom Mrz 2/373 u miševa trovanih somanom. Radi dobijanja parametara zaštitne efikasnosti antidota, albino miševima mužjacima su iv aplikovane rastuće doze antidota u određenim vremenskim intervalima ( 1 -60 min) pre 1,3 LD-50 iv somana. Aktivnosti acetilholinesteraze mozga, dijafragme i eritrocita, kao i karboksilesteraza plazme, određivane su nakon iv primene adamantana (10 mg/kg) i/ili oksima HI-6 (3,1 mg/kg; 7,96 µmol/kg) datih 5 min pre 0,75 LD-50 iv somana. Primena oksima HI-6 je obezbedila najbolju zaštitu eksperimentalnih životinja, a srednja efektivna doza u nultom vremenu ED-500 iznosila je 7,96 µmol/kg. Kada je primenjen u kombinaciji sa oksimima, memantin je doveo do značajnog (oko 9 puta) smanjenja HD-500 vrednosti svih oksima, osim trimedoksima. ali je zato poluvreme efikasnosti trimedoksima povećano 4,82 puta. Značajan porast acetilholinesteraze dijafragme dobijen je primenom HI-6, memantina kao i njihove kombinacije. U odnosu na grupu koja je primila samo soman, aktivnost acetilholi­nesteraze eritrocita bila je značajno veća u grupama kojima su davani adamantani i/ili HI-6. Nijedan od primenjenih tretmana nije doveo do statistički značajnog povećanja aktivnosti acetilholinesteraze mozga i karboksilesteraza plazme. Bolji zaštitni efekt kombinacija oksima i memantina u odnosu na same oksime mogao bi se pripisati antikonvulzivnom potencijalu memantina, koji je nekompetitivni antagonista NMDA receptora, ali i izvesnoj zaštiti aktivnog centra acetilholinesteraze dijafragme.",
publisher = "Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd",
journal = "Archives of Toxicology, Kinetics and Xenobiotic Metabolism",
title = "Potential beneficial action of adamantanes in mice poisoned with soman, Potencijalna uloga adamantana u trovanju miševa somanom",
volume = "9",
number = "1-2",
pages = "13-20",
url = "https://hdl.handle.net/21.15107/rcub_farfar_305"
}
Antonijević, B., Maksimović, M., Kilibarda, V., Stojiljković, M. P., Nedeljković, M., Milovanović, Z. A.,& Bokonjić, D.. (2001). Potential beneficial action of adamantanes in mice poisoned with soman. in Archives of Toxicology, Kinetics and Xenobiotic Metabolism
Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd., 9(1-2), 13-20.
https://hdl.handle.net/21.15107/rcub_farfar_305
Antonijević B, Maksimović M, Kilibarda V, Stojiljković MP, Nedeljković M, Milovanović ZA, Bokonjić D. Potential beneficial action of adamantanes in mice poisoned with soman. in Archives of Toxicology, Kinetics and Xenobiotic Metabolism. 2001;9(1-2):13-20.
https://hdl.handle.net/21.15107/rcub_farfar_305 .
Antonijević, Biljana, Maksimović, Matej, Kilibarda, Vesna, Stojiljković, Miloš P., Nedeljković, Mirjana, Milovanović, Zoran A., Bokonjić, Dubravko, "Potential beneficial action of adamantanes in mice poisoned with soman" in Archives of Toxicology, Kinetics and Xenobiotic Metabolism, 9, no. 1-2 (2001):13-20,
https://hdl.handle.net/21.15107/rcub_farfar_305 .

Protective effects of memantine and pyridinium oximes in mice poisoned with dichlorvos

Antonijević, Biljana; Maksimović, M.; Stojiljković, Miloš P.; Nedeljković, Mirjana; Đukić, Mirjana

(Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd, 2000)

TY  - JOUR
AU  - Antonijević, Biljana
AU  - Maksimović, M.
AU  - Stojiljković, Miloš P.
AU  - Nedeljković, Mirjana
AU  - Đukić, Mirjana
PY  - 2000
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/274
PB  - Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd
T2  - Archives of Toxicology, Kinetics and Xenobiotic Metabolism
T1  - Protective effects of memantine and pyridinium oximes in mice poisoned with dichlorvos
T1  - Zaštitni efekti memantina i piridinijumskih oksima u miševa trovanih dihlorvosom
VL  - 8
IS  - 3
SP  - 216
EP  - 217
UR  - https://hdl.handle.net/21.15107/rcub_farfar_274
ER  - 
@article{
author = "Antonijević, Biljana and Maksimović, M. and Stojiljković, Miloš P. and Nedeljković, Mirjana and Đukić, Mirjana",
year = "2000",
publisher = "Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd",
journal = "Archives of Toxicology, Kinetics and Xenobiotic Metabolism",
title = "Protective effects of memantine and pyridinium oximes in mice poisoned with dichlorvos, Zaštitni efekti memantina i piridinijumskih oksima u miševa trovanih dihlorvosom",
volume = "8",
number = "3",
pages = "216-217",
url = "https://hdl.handle.net/21.15107/rcub_farfar_274"
}
Antonijević, B., Maksimović, M., Stojiljković, M. P., Nedeljković, M.,& Đukić, M.. (2000). Protective effects of memantine and pyridinium oximes in mice poisoned with dichlorvos. in Archives of Toxicology, Kinetics and Xenobiotic Metabolism
Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd., 8(3), 216-217.
https://hdl.handle.net/21.15107/rcub_farfar_274
Antonijević B, Maksimović M, Stojiljković MP, Nedeljković M, Đukić M. Protective effects of memantine and pyridinium oximes in mice poisoned with dichlorvos. in Archives of Toxicology, Kinetics and Xenobiotic Metabolism. 2000;8(3):216-217.
https://hdl.handle.net/21.15107/rcub_farfar_274 .
Antonijević, Biljana, Maksimović, M., Stojiljković, Miloš P., Nedeljković, Mirjana, Đukić, Mirjana, "Protective effects of memantine and pyridinium oximes in mice poisoned with dichlorvos" in Archives of Toxicology, Kinetics and Xenobiotic Metabolism, 8, no. 3 (2000):216-217,
https://hdl.handle.net/21.15107/rcub_farfar_274 .

Modification of the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase of hen brain

Jokanović, Milan; Stepanović-Petrović, Radica; Maksimović, Matej; Kosanović, Melita; Stojiljković, Miloš P.

(Elsevier Sci Ireland Ltd, Clare, 1998)

TY  - JOUR
AU  - Jokanović, Milan
AU  - Stepanović-Petrović, Radica
AU  - Maksimović, Matej
AU  - Kosanović, Melita
AU  - Stojiljković, Miloš P.
PY  - 1998
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/174
AB  - This study was aimed to investigate the possibility of modifying the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase (NTE) of hen blain. This reaction on NTE occurs with a half-time of 7.4 min. Atropine was effective in decreasing the rate of aging on DFP-inhibited NTE and this effect was time-and concentration-dependent. Atropine was also a weak but progressive inhibitor of NTE activity (I-50 = 80 mM) and this reaction appears to be reversible at lower atropine concentrations. Among compounds containing oxime functional groups only OPAB, having longer methylene chain and being more lipophylic than other oximes usually used in acetylcholinesterase (AChE) reactivation studies, was effective in decreasing the rate of aging on DFP-inhibited NTE. However, when atropine and oximes were used together we have obtained a potentiating and/or synergistic effect which was most significant with combination of atropine and TMB-4 giving up to a 15-fold decrease in the rate of aging reaction. The efficacy of this particular combination was concentration-dependent. We have also discussed similarities and differences in aging reaction occurring on NTE and AChE.
PB  - Elsevier Sci Ireland Ltd, Clare
T2  - Toxicology Letters
T1  - Modification of the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase of hen brain
VL  - 95
IS  - 2
SP  - 93
EP  - 101
DO  - 10.1016/S0378-4274(98)00017-4
ER  - 
@article{
author = "Jokanović, Milan and Stepanović-Petrović, Radica and Maksimović, Matej and Kosanović, Melita and Stojiljković, Miloš P.",
year = "1998",
abstract = "This study was aimed to investigate the possibility of modifying the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase (NTE) of hen blain. This reaction on NTE occurs with a half-time of 7.4 min. Atropine was effective in decreasing the rate of aging on DFP-inhibited NTE and this effect was time-and concentration-dependent. Atropine was also a weak but progressive inhibitor of NTE activity (I-50 = 80 mM) and this reaction appears to be reversible at lower atropine concentrations. Among compounds containing oxime functional groups only OPAB, having longer methylene chain and being more lipophylic than other oximes usually used in acetylcholinesterase (AChE) reactivation studies, was effective in decreasing the rate of aging on DFP-inhibited NTE. However, when atropine and oximes were used together we have obtained a potentiating and/or synergistic effect which was most significant with combination of atropine and TMB-4 giving up to a 15-fold decrease in the rate of aging reaction. The efficacy of this particular combination was concentration-dependent. We have also discussed similarities and differences in aging reaction occurring on NTE and AChE.",
publisher = "Elsevier Sci Ireland Ltd, Clare",
journal = "Toxicology Letters",
title = "Modification of the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase of hen brain",
volume = "95",
number = "2",
pages = "93-101",
doi = "10.1016/S0378-4274(98)00017-4"
}
Jokanović, M., Stepanović-Petrović, R., Maksimović, M., Kosanović, M.,& Stojiljković, M. P.. (1998). Modification of the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase of hen brain. in Toxicology Letters
Elsevier Sci Ireland Ltd, Clare., 95(2), 93-101.
https://doi.org/10.1016/S0378-4274(98)00017-4
Jokanović M, Stepanović-Petrović R, Maksimović M, Kosanović M, Stojiljković MP. Modification of the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase of hen brain. in Toxicology Letters. 1998;95(2):93-101.
doi:10.1016/S0378-4274(98)00017-4 .
Jokanović, Milan, Stepanović-Petrović, Radica, Maksimović, Matej, Kosanović, Melita, Stojiljković, Miloš P., "Modification of the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase of hen brain" in Toxicology Letters, 95, no. 2 (1998):93-101,
https://doi.org/10.1016/S0378-4274(98)00017-4 . .
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