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ATROPINE-4-OXIME: IN VIVO EVALUATION OF ITS ANTIDOTAL EFFICACY


Berend, Suzana; Lucić Vrdoljak, Ana; Radić, Božica; Lovrić, Jasna
ATROPINE-4-OXIME: IN VIVO EVALUATION OF ITS ANTIDOTAL EFFICACY // 10th International Meeting on Cholinesterases, Šibenik, Croatia, Programme and Abstracts / Kovarik, Zrinka (ur.).
Zagreb: Hrvatsko društvo za biokemiju i molekularnu biologiju, 2009. str. 111-111 (poster, međunarodna recenzija, sažetak, znanstveni)


Naslov
ATROPINE-4-OXIME: IN VIVO EVALUATION OF ITS ANTIDOTAL EFFICACY

Autori
Berend, Suzana ; Lucić Vrdoljak, Ana ; Radić, Božica ; Lovrić, Jasna

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
10th International Meeting on Cholinesterases, Šibenik, Croatia, Programme and Abstracts / Kovarik, Zrinka - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju, 2009, 111-111

Skup
10th International Meeting on Cholinesterases

Mjesto i datum
Šibenik, Hrvatska, 20.-25.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Atropine-4-oxime; OP compounds; therapy

Sažetak
Improving the efficacy of antidotal treatment of poisonings with organophosphorous compounds (OPc) is still challenge for the scientific community. OPc are widely used as pesticides, as drugs in the treatment of cholinergic disorders, and as nerve agents in chemical warfare. Irreversible inhibition of acetylcholinesterase (AChE) by these compounds results in acethylcholine (ACh) accumulation in the synaptic cleft with consequences to the central and peripheral nervous system. The clinical signs of AChE inhibition manifest as hypersalivation, lacrimation, diarrhea, tremor, respiratory distress, convulsions, and seizures. Signs are dose-dependent, leading to severe incapacitation and rapid death. Presently, OPc poisoning is treated with a combination of an antimuscarinic agent, e.g. atropine and an AChE reactivator oxime. In this study a new compound atropine-4-oxime (synthesis not yet published), was tested as potential antidote in vivo in the therapy of soman, tabun and paraoxon intoxication in mice. Currently used oximes HI-6 and TMB-4 were included for comparison. The studied compounds (5 or 25 % of their LD50) plus atropine (10 mg/kg) were given intraperitoneally one minute after OPc (given subcutaneously). Their therapeutic efficacy was expressed as protective index (PI) and maximal dose of poison (MDP). Atropine-4-oxime showed very weak antidotal activity inadequate for soman or tabun poisoning. On the other hand, it was very effective at both applied doses upon paraoxon poisoning, showing survival of all animals after administration of 10.0, that is 15.9 LD50 of paraoxon. As well as HI-6 and TMB-4, atropine-4-oxime appear to be suitable for the antidotal treatment of acute paraoxon poisonings, regardless of its high toxicity.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
022-0222148-2139 - Terapijski učinak novosintetiziranih spojeva pri otrovanju organofosfatima (Ana Lucić Vrdoljak, )

Ustanove
Institut za medicinska istraživanja i medicinu rada, Zagreb