Naslov
New byspiridinium oximes:in vitro evaluation of their biochemical parameters

Autori
Berend, Suzana ; Lucić Vrdoljak, Ana ; Radić, Božica ; Kuča, Kamil

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

Izvornik
The IXth International Meeting on Cholinesterases : program and abstracts book / - Suzhou, 2007, 138-138

Skup
International Meeting on Cholinesterases (9 ; 2007)

Mjesto i datum
Suzhou, Kina, 06.05.2007. - 10.05.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
byspiridinium oximes; acetylcholinesterase; nerve agents;

Sažetak
Improving the efficacy of antidotal treatment of poisonings with nerve agents is still very important task. Organophosphates-nerve agents are characterized as compounds influencing cholinergic nerve transmission via inhibition of acetylcholinesterase (AChE), an extremely active enzyme that hydrolyses acetylcholin. The clinical signs of AChE inhibition manifest as hypersalivation, lacrimation, diarrhoea, tremor, respiratory distress, convulsions and seizures. Signs are dose-dependent, leading to severe incapacitation and rapid death. Pyridinium oximes are nowadays used as successful treatment of poisoning with many organophosphates. Reason for that lies in the mechanism of oxime activity, which is based on protection of unphosphorylated AChE and/or reactivation of phosphorylated AChE. The aim of this investigation was to define the biochemical parameters of three bispyridinium oximes K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide], K033 [1, 4-bis (2-hydroxyiminomethylpyridinium) butane dibromide] and K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide]. For each of the compounds it was determined the toxic effect on human erythrocytes AChE in vitro (IC50) and their reactivating (%R) and protective potency (P50) with respect to soman- and tabun- inhibited AChE. Earlier we described in vivo antidotal activity of tested oximes against soman and tabun in male mice. The new tested oximes were toxic to human erythrocytes AChE ; in decreasing order from K033, K048 to K027. IC50 ranged from 0.02 to 1.0 mM. The best reactivating potency was obtained with K048 when AChE was inhibited by tabun. The protective potency of all oximes on human erythrocytes AChE inhibited by soman and tabun could not be determined. Our results indicate a good affinity of the tested compounds for AChE. The oximes are reversible ihibitors of AChE in vitro and show pharmacological properties which are related to reactivation of AChE.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA