Pralidoxime iodide (2-PAM) penetrates across the blood-brain barrier

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-depen...

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Veröffentlicht in:Neurochemical research 2003-09, Vol.28 (9), p.1401-1407
Hauptverfasser: SAKURADA, Koichi, MATSUBARA, Kazuo, SHIMIZU, Keiko, SHIONO, Hiroshi, SETO, Yasuo, TSUGE, Koichiro, YOSHINO, Mineo, SAKAI, Ikuko, MUKOYAMA, Harutaka, TAKATORI, Takehiko
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Sprache:eng
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Zusammenfassung: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.
ISSN:0364-3190
1573-6903
DOI:10.1023/A:1024960819430