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-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.
Sakurada
Koichi
K
National Research Institute of Police Science, 6-3-1, Kashiwanoha, Kashiwa-city, Chiba 277-0880, Japan. sakurada@nrips.go.jp
Matsubara
Kazuo
K
Shimizu
Keiko
K
Shiono
Hiroshi
H
Seto
Yasuo
Y
Tsuge
Koichiro
K
Yoshino
Mineo
M
Sakai
Ikuko
I
Mukoyama
Harutaka
H
Takatori
Takehiko
T
D026905:Amino Acid Transport Systems / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000378:metabolism / Q000493:pharmacokinetics*; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002801:Cholinesterase Reactivators / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D008239:Lysine / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D011220:Pralidoxime Compounds / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D014633:Valine / Q000494:pharmacology
D026905:Amino Acid Transport Systems; D000931:Antidotes; D002801:Cholinesterase Reactivators; D011220:Pralidoxime Compounds; D014633:Valine; D008239:Lysine; C028797:pralidoxime