title: Partition of bispyridinium oximes (trimedoxime and K074) administered in therapeutic doses into different parts of the rat brain.
abstract: The penetration of acetylcholinesterase reactivators (oximes) into the central nervous system is typically restricted by the blood-brain barrier. Although oximes are highly hydrophilic compounds, some contradictory results confirming permeation into the brain exist. The aim of this study is to verify the penetration of oximes through the blood-brain barrier and to detect their levels achieved in different brain regions 60 min after the administration. It was confirmed that oximes are able to penetrate into the brain after injection of therapeutic doses corresponding with 5% of LD(50). The level in whole brain was 0.58% for trimedoxime and 0.85% for the experimental drug oxime K074 as the percentage of their plasma concentration. The highest concentration was found in frontal cortex (trimedoxime 2.27%; oxime K074 0.95%) and lowest in basal ganglia (trimedoxime 0.86%; oxime K074 0.42%). Entry of oximes into the brain is minimal, but some low reactivation effect should be expected. The reactivation potency of oximes might be higher or lower, depending on the real oxime concentration in a given area.
authors.affiliation: Department of Public Health, Faculty of Military Health Sciences, Trebesska 1575, Hradec Kralove, Czech Republic. karasova@pmfhk.cz
authors.forename: Jana Zdarova
authors.initials: JZ
authors.lastname: Karasova
authors.forename: Filip
authors.initials: F
authors.lastname: Zemek
authors.forename: Jiri
authors.initials: J
authors.lastname: Bajgar
authors.forename: Martina
authors.initials: M
authors.lastname: Vasatova
authors.forename: Petr
authors.initials: P
authors.lastname: Prochazka
authors.forename: Ladislav
authors.initials: L
authors.lastname: Novotny
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002073:Butanes / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology; D002138:Calibration; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation; D007273:Injections, Intramuscular; D057230:Limit of Detection; D008297:Male; D015394:Molecular Structure; D010091:Oximes / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D012044:Regression Analysis; D015203:Reproducibility of Results; D014018:Tissue Distribution; D014289:Trimedoxime / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C515196:1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide; D002073:Butanes; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D014289:Trimedoxime