Naslov
Antidotal efficacy of pyridinium chloride derivatives against soman poisoning

Autori
Lucić Vrdoljak, Ana ; Lovrić, Jasna ; Radić, Božica ; Žlender, Vilim

Izvornik
Pharmacology & Toxicology (0901-9928) 99 (2006); 17-21

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Pyridinium chloride derivatives; antidotes; soman poisoning; AChE

Sažetak
Acetylcholinesterase (AChE ; EC 3.1.1.7.) is an extremely active enzyme necessary for terminating the action of acetylcholine in cholinergic synapses. The aim of this study was to evaluate the efficacy of four mono-pyridinium compounds 1-phenacylpyridinium chloride (I), 1-phenacyl-2-methylpyiridinium chloride (II), 1-benzoylethylpyridinium chloride (III), and 1-benzoylethylpyridinium-4-aldoxime chloride (IV) in the therapy of soman poisoning. Their effect was compared with HI-6 and TMB-4 oximes. The inhibitory potency (IC50) of compounds as well as reactivating (%R) and protective potency (P50) with respect to soman-inhibited AChE were determined for each of the compounds. Their acute intraperitoneal (i.p.) toxicity (LD50 with 95% confidence limits) was tested in mice and observed for 24 hours. The therapeutic effect was expressed as the protective index (PI) and as the therapeutic dose (TD). The tested compounds were found to be reversible inhibitors of AChE. In vivo results show that the tested compounds are relatively toxic (their LD50 was from 74.9 to 210.0 mg/kg body weight). The best antidotal efficacy was obtained with compound II, which had the highest affinity for AChE (IC50 was 1.9 x 10-5 mol L-1) and seems to be an adequate antidote in soman poisoning (its PI and TD were 2.8 and 2, respectively). Our results indicate that its antidotal effect is related to the reactivation or protection of AChE. The type of the substituent in the pyridinium ring generally has a significant influence on toxicity in vitro and in vivo, and on the antidotal efficacy of all new tested compounds.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

Napomena
*naziv časopisa: Basic & Clinical Pharmacology & Toxicology ISSN 1742-7835

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