Pralidoxime iodide (2-pAM) penetrates across the blood-brain barrier |
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Authors: | Sakurada Koichi Matsubara Kazuo Shimizu Keiko Shiono Hiroshi Seto Yasuo Tsuge Koichiro Yoshino Mineo Sakai Ikuko Mukoyama Harutaka Takatori Takehiko |
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Institution: | (1) National Research Institute of Police Science, 6-3-1, Kashiwanoha, Kashiwa-city, Chiba, 277-0880, Japan;(2) Departments of Hospital Pharmacy & Pharmacology or Leagal Medicine, Asahikawa Medical College, Asahikawa, 078-8510, Japan |
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Abstract: | 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. |
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Keywords: | 2-PAM blood-brain barrier microdialysis acetylcholinesterase sarin |
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