title: Mini review on blood-brain barrier penetration of pyridinium aldoximes.
abstract: This paper reviews the blood-brain barrier (BBB) penetration of newly developed pyridinium aldoximes. Pyridinium aldoximes are highly charged hydrophilic compounds used in the treatment of subjects exposed to organophosphonates because they are effective as acetylcholinesterase reactivators. Pyridinium aldoximes have antidotal effects against poisoning with cholinesterase inhibitors, a frequent problem affecting people working with organophosphate-based insecticides and pesticides. Toxic organophosphonate products such as sarin and tabun can be used by terrorists as chemical warfare agents. This poses a severe challenge to all innocent and peace-loving people worldwide. This review gives a brief summary of BBB transporters and description of the current in vitro and in vivo methods for the characterization of BBB penetration of established and novel pyridinium aldoximes. The authors provide a putative mechanism of penetration, outline some future ways of formulation and discuss the possible advantages and disadvantages of increasing BBB penetration.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089, Budapest, Nagyvárad tér 4, Hungary; Department of Pharmacology and Therapeutics, CMHS, United Arab Emirates University, Al Ain, P.O.Box 17666, United Arab Emirates.
authors.forename: H
authors.initials: H
authors.lastname: Kalász
authors.forename: S M
authors.initials: SM
authors.lastname: Nurulain
authors.forename: G
authors.initials: G
authors.lastname: Veress
authors.forename: S
authors.initials: S
authors.lastname: Antus
authors.forename: F
authors.initials: F
authors.lastname: Darvas
authors.forename: E
authors.initials: E
authors.lastname: Adeghate
authors.forename: A
authors.initials: A
authors.lastname: Adem
authors.forename: F
authors.initials: F
authors.lastname: Hashemi
authors.forename: K
authors.initials: K
authors.lastname: Tekes
mesh_terms: D000818:Animals; D000931:Antidotes / Q000493:pharmacokinetics / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002801:Cholinesterase Reactivators / Q000493:pharmacokinetics*; D006801:Humans; D062025:Organophosphate Poisoning / Q000188:drug therapy; D010091:Oximes / Q000493:pharmacokinetics*; D011726:Pyridinium Compounds / Q000493:pharmacokinetics*
chemical_list: D000931:Antidotes; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds
keywords: K027; K203; blood-brain barrier; cerebrospinal fluid; penetration; pralidoxime; pyridinium aldoximes; rat