Sakurada Koichi, Matsubara Kazuo, Shimizu Keiko, Shiono Hiroshi, Seto Yasuo, Tsuge Koichiro, Yoshino Mineo, Sakai Ikuko, Mukoyama Harutaka, Takatori Takehiko
National Research Institute of Police Science, 6-3-1, Kashiwanoha, Kashiwa-city, Chiba 277-0880, Japan.
Neurochem Res. 2003 Sep;28(9):1401-7. doi: 10.1023/a:1024960819430.
The in vivo rat brain microdialysis technique with HPLC/UV was used to determine the blood-brain barrier (BBB) penetration of pralidoxime iodide (2-PAM), which is a component of the current nerve agent antidote therapy. After intravenous dosage of 2-PAM (10, 50, 100 mg/kg), 2-PAM appeared dose-dependently in the dialysate; the striatal extracellular/blood concentration ratio at 1 h after 50 mg/kg dosage was 0.093 +/- 0.053 (mean +/- SEM). This finding offered conclusive evidence of the BBB penetration of 2-PAM. We also examined whether the BBB penetration of 2-PAM was mediated by a certain specific transporter, such as a neutral or basic amino acid transport system. Although it was unclear, the neural uptake of 2-PAM was Na+ dependent. The mean BBB penetration by 2-PAM was approximately 10%, indicating the intravenous administration of 2-PAM might be to a degree effective to reactivation of the blocked cholinesterase in the brain.
