VZL 2010, 79(1):23-27

Is Oxime Fluorination the Proper Way to Increase Penetration of These Compounds in the Central Nervous System?

Jana Žďárová Karasová ORCID...1, Jiří Kassa ORCID...1, Kamil Musílek ORCID...1, Young-Sik Jung3, Kamil Kuča ORCID...2
1 Univerzita obrany, Fakulta vojenského zdravotnictví, katedra toxikologie, Hradec Králové
2 Univerzita obrany, Fakulta vojenského zdravotnictví, Centrum pokročilých studií, Hradec Králové
3 Korea Research Institute of Chemical Technology, Medicinal Science Division, Daejeon, Korea

Přestup reaktivátorů acetylcholinesterasy přes hematoencefalickou bariéru je v současnosti jedním z často debatovaných problémů souvisejících s účinností těchto terapeutik. Zvýšení lipofility se jeví jako jedna z možných cest, které by mohly zvýšit průnik těchto látek do mozku.
V této práci je hodnocena reaktivační účinnost nově připraveného oximu - fluorovaného reaktivátoru K203, který byl připraven na spolupracujícím pracovišti Research Institute of Chemical Technology (Korea) a nese označení K22836. Fluorace oximu K203 však vedla k snížení jeho terapeutické účinnosti, která se projevila jak snížením reaktivace acetylcholinesterasy v krvi, tak i v centrálním nervovém systému. Nejlépe působícím reaktivátorem vůči tabunem inhibované acetylcholinesterase tak i nadále zůstává původní, námi připravený oxim K203.

Keywords: Reaktivátor; AChE; K203; K22836; CNS

The penetration of acetylcholinesterase (AChE) reactivators through the blood-brain barrier is hotly discussed question nowadays. The increase of lipophilicity of these compounds is one of the possible ways how to increase their penetration and also their efficacy in the central nervous system.The aim of this study is to compare the reactivation potency of newly synthesized oxime - oxime K203 - after its fluorination. This AChE reactivator was prepared at the Research Institute of Chemical Technology (Korea) and is known as K22836. The fluorination of oxime K203 leads to reduction of its therapeutic efficacy. The reactivation potency of newly synthesized oxime K22836 was lower in the whole blood and also in the central nervous system. In summary, the most efficacious reactivator in case of tabun-inhibited AChE is still oxime K203 originally prepared at our department.

Keywords: Reactivator; AChE; K203; K22836; CNS

Received: April 27, 2009; Published: March 1, 2010  Show citation

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Žďárová Karasová, J., Kassa, J., Musílek, K., Jung, Y., & Kuča, K. (2010). Is Oxime Fluorination the Proper Way to Increase Penetration of These Compounds in the Central Nervous System? Vojenské Zdravotnické Listy, 79(1), 23-27
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