Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos
Датум
2011
Наслов журнала
Журнал ISSN
Наслов волумена
Издавач
Ministry of Defance, Serbia
Апстракт
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 moL/kg in soman poisoning) and obidoxime (16.80 vs 2.75 moL/kg in dichlorvos poisoning; 21.56 vs 6.63 moL/kg in heptenophos poisoning). Memantine and midazolam succeded 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
Опис
Кључне речи
organophosphorus compounds; poisoning; antidotes; oximes; memantine; obidoxime chloride; anticonvulsants