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ANTIDOTAL EFFICACY OF BISPYRIDINIUM OXIME K027 AGAINST TABUN POISONING (CROSBI ID 556631)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija

Radić, Božica ; Berend, Suzana ; Lucić Vrdoljak, Ana ANTIDOTAL EFFICACY OF BISPYRIDINIUM OXIME K027 AGAINST TABUN POISONING // 10th International Meeting on Cholinesterases, Šibenik, Croatia, Programme and Abstracts / Kovarik, Zrinka (ur.). Zagreb: Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2009. str. 111-112

Podaci o odgovornosti

Radić, Božica ; Berend, Suzana ; Lucić Vrdoljak, Ana

engleski

ANTIDOTAL EFFICACY OF BISPYRIDINIUM OXIME K027 AGAINST TABUN POISONING

A toxic effect of highly toxic nervous warfare agents is irreversible inhibition of vitaly important enzyme acethylcholinesterase (AChE). Inhibition of AChE results in accumulation of acetylcholine (ACh) at the synaptic cleft of the cholinergic neurones, leading to overstimulation of cholinergic receptors. The highly toxic nature of tabun has been known for many years, but there are still serious limitations to the antidotal therapy. Tabun-phosphorylated AChE is resistant to oxime reactivation due to an electron pair located on the amidic group that makes the nucleophilic attack almost impossible . The current standard treatment for poisoning by OP compounds includes the combined administration of cholinesterase reactivatior (oxime), a muscarinic cholinergic receptor antagonist (atropine sulphate) and pre-treatment with reversible carbamate AChE-inhibitor, such as pyridostigmine. The inability of the standard therapy to provide adequate protection against tabun calls for a synthesis of new compounds with the characteristic oxime group. In this paper a new bis-pyridinium compound K027 [1-(4-hidroxyiminomethylpyridinium)-3-(-4-carbamoylpyridinium) propane] was tested as potential antidote in tabun poisoned mice. In all experiments, oxime K027 in dose of ¼ of its LD50 was used as pretreatment 15 min before tabun intoxication, and ¼ LD50 of oximes K027, K048 or TMB-4 together with atropine as therapy one minute after tabun poisoning. The antidotal efficacy of tested compound was expressed as protection index (PI) and maximal dose of poison (MDP). In this study the best result was obtained with the therapeutic regimen consisting of ¼ LD50 of K027 as pretreatment and ¼ of LD50 of K027 or K048 plus atropine as therapy. MDP was 7.9 LD50 of tabun with survival of all tested animals. Under these experimental conditions oxime K027 demonstrated an improvement in treatment over the therapy with oxime plus atropine or pretreatment alone. Herein we show that already promising treatment in tabun poisoning by oximes and atropine could be improved if oximes are also used in pretreatment.

bispyridinuim oxime K027; tabun; therapy

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Podaci o prilogu

111-112.

2009.

objavljeno

Podaci o matičnoj publikaciji

10th International Meeting on Cholinesterases, Šibenik, Croatia, Programme and Abstracts

Kovarik, Zrinka

Zagreb: Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB)

Podaci o skupu

10th International Meeting on Cholinesterases

poster

20.09.2009-25.09.2009

Šibenik, Hrvatska

Povezanost rada

Temeljne medicinske znanosti