MMSL 2019, 88(3):121-133 | DOI: 10.31482/mmsl.2019.016

PROPHYLACTIC AGENTS IN THE MANAGEMENT OF ORGANOPHOSPHORUS INTOXICATIONReview article

Barbora Svobodová ORCID...1,2, Lukáš Górecki ORCID...1,2, Jan Korábečný ORCID...1,2*
1 Katedra toxikologie a vojenské farmacie, Fakulta vojenského zdravotnictví, Univerzita obrany v Brně, Třebešská 1575, 500 02, Hradec Králové, Česká republika
2 Centrum biomedicínského výzkumu, Fakultní nemocnice Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Česká republika

Nervově paralytické látky (NPL) patří mezi organofosforové inhibitory (OFI) acetylcholinesterasy (AChE). Přestože je používání vysoce toxických OFI jako chemických bojových látek zakázáno, byly tyto látky v minulosti několikrát zneužity. Z těchto důvodů je vývoj nových profylakticky účinných sloučenin a terapie intoxikací OFI stále aktuální. Podáním běžných antidot (např. oximových reaktivátorů) profylakticky se nejen zvyšuje odolnost organismu proti účinkům NPL při očekávané intoxikaci, např. při práci v zamořeném prostředí po teroristickém útoku, ale potencuje se i následná antidotní léčba po expozici. Farmakologická profylaxe se v současnosti dá rozdělit na tři směry – ochrana AChE před ireverzibilní inhibicí, profylaktické podání běžných antidot a použití tzv. bioscavengerů nebo-li "vychytávačů" OFI. Cílem předkládaného přehledového článku je poukázat na současné trendy profylaxe a zároveň nastínit vývoj nových potenciálních reverzibilních inhibitorů AChE, jako jsou např. huperzin A či akridinové deriváty.

Keywords: nervově paralytické látky; profylaktická antidota; acetylcholinesterasa; takrin; huperzin A; profylaxe

Nerve agents (NAs) belong to family of organophosphorus inhibitors (OPIs) of acetylcholinesterase (AChE) enzyme. Although the use of highly toxic OPIs as chemical warfare agents is prohibited, they have been misused several times and thus still represents an emerging threat. For these reasons, the development of novel prophylactic agents and therapeutic intervention against NAs is still up-to-date and of high importance. Prophylactic administration of antidotes not only increases body's resistance to the effects of NAa, e.g. when operating at a contaminated environment after a terrorist attack, but also potentiates the subsequent antidotal therapy after exposure. Currently, pharmacological prophylaxis can be delivered either by protection of AChE against irreversible Inhibition, administration of commonly used antidotes in advance (i.e. oxime reactivators) or by the use of bioscavengers. The aim of the recent review is to highlight the current trends in prophylaxis and outline breakthroughs in prophylaxis based on reversible cholinesterase inhibitors like huperzine A or acridine derivatives.

Keywords: nerve agents; prophylactic antidotes; acetylcholinesterase; tacrine; huperzine A; prophylaxis

Received: June 24, 2019; Accepted: June 24, 2019; Prepublished online: July 31, 2019; Published: September 6, 2019  Show citation

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Svobodová, B., Górecki, L., & Korábečný, J. (2019). PROPHYLACTIC AGENTS IN THE MANAGEMENT OF ORGANOPHOSPHORUS INTOXICATION. MMSL, 88(3), 121-133. doi: 10.31482/mmsl.2019.016
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