Improved delivery through biological membranes. 3. Delivery of N-methylpyridinium-2-carbaldoxime chloride through the blood-brain barrier in its dihydropyridine pro-drug form.
Administration of N-methyl-1,6-dihydropyridine-2-carbaldoxime hydrochloride, the pro-drug form of 2-PAM, resulted in an average of 13-fold increase in the amount of 2-PAM delivered into the brain of mice as compared to the administration of 2-PAM. The pro-drug which crossed the BBB resulted in a dramatic increase in the reactivation of AChE blocked by DFP. In vivo studies of the "aging" of the phosphorylated AChE in the brain of mice could also be studied using pro-2-PAM.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002801:Cholinesterase Reactivators; D004456:Echothiophate Iodide / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011220:Pralidoxime Compounds / Q000378:metabolism* / Q000494:pharmacology
D002801:Cholinesterase Reactivators; D011220:Pralidoxime Compounds; D004456:Echothiophate Iodide; D000110:Acetylcholinesterase