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Penetration of polar organic compounds through the blood-brain barrier
BMC Pharmacology volume 11, Article number: A51 (2011)
The effect of polar organic xenobiotics in the central nervous system depends on blood-brain barrier (BBB) penetration of these compounds. Newly synthesized pyridinium aldoximes (K-compounds) are promising antidotes for organophosphate intoxications. However, being highly polar, their BBB penetration is questionable. Using an in vivo model we aimed to characterize the BBB penetration of K-compounds.
Male Wistar rats were injected intramuscularly with various doses of pyridinium aldoximes, blood, cerebrospinal fluid (CSF), and brain samples were collected after 5, 15, 30, 60 and 180 min. A recently developed and optimized RP-HPLC method was used for analysis. Samples of brain homogenate, blood serum and CSF were subjected to clean-up using precipitation by perchloric acid (pH < 1) and centrifugation at 14,000 rpm at 4°C for 20 min. Before load onto Zorbax Rx-C18 stationary phase, the pH of the supernatants was adjusted to 2. As mobile phase a mixture of acetonitrile and aqueous buffer pH 4.5, also containing ion-pairing agent, was used.
Dose- and time-dependent BBB penetration of pyridinium aldoximes was experimentally found.
Dose- and time-dependent brain and CSF levels of these highly polar K-compounds following intramuscular administration suggest contribution of active transport or specific transporters in their BBB penetration. The BBB transport may also depend on the size and charge of the solutes.
The authors are grateful to Ms. Györgyike Guth for her skilful technical assistance.
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Kalász, H., Musílek, K. & Tekes, K. Penetration of polar organic compounds through the blood-brain barrier. BMC Pharmacol 11 (Suppl 2), A51 (2011). https://doi.org/10.1186/1471-2210-11-S2-A51
- Active Transport
- Blood Serum
- Perchloric Acid
- Brain Sample
- Brain Homogenate