J Appl Biomed 8:35-40, 2010 | DOI: 10.2478/v10136-009-0005-9

In vitro screening of blood-brain barrier penetration of clinically used acetylcholinesterase reactivators

Jana Žďárová Karasová^1,*, Petr Stodůlka², Kamil Kuča^1,2

¹ Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic

² Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic

In this in vitro study, using the HPLC method, we determined the ability of acetylcholinesterase (AChE) reactivators, used clinically, to penetrate the blood-brain barrier (BBB). We evaluated pralidoxime, HI-6, obidoxime, trimedoxime and methoxime - reactivators varying in the position of the oxime group on the pyridinium ring and linker connecting the pyridinium rings. Our results indicated that pralidoxime, a monoquaternary AChE reactivator, was the oxime with the most penetration. Molecular weight seems to be the most important factor for passive transport through the BBB. From the structural perspective, the connecting linker also plays a key role in the ability of the reactivators to penetrate the CNS. In this case, the simple and short linker is favorable for permeation of these compounds. The location of the oxime group on the pyridine ring may also influence passive transport into the brain; the best position of the oxime group seems to be position four.

Keywords: blood-brain barrier; CNS penetration; HI-6; obidoxime; HPLC; oxime

Received: June 23, 2009; Revised: September 10, 2009; Published: March 31, 2010  Show citation