title: The history of cholinesterase reactivation: hydroxylamine and pyridinium aldoximes.
abstract: Hydroxylamine (NH2OH) the substance which will turn out to be of importance to those interested in the treatment of organophosporus cholinesterase inhibitor exposure, was synthesized by Wilhem Clemens Lossen in 1865 while working in Halle as an assistant in the laboratory of Wilhelm Heinrich Heintz. The Lossen synthesis generated hydroxylamine in aqueous solution. Anhydrous hydroxylamine was prepared almost simultaneously by Lobry de Bruyn and Crismer (1891). Using hydroxylamine as a starting point Meyer synthesized aldoximes and ketoximes (1897). Lange, a PhD student of Ladenburg, isolated 2-methyl-pyridine (alpha-picoline). Some fifty years later Wilson, working in the laboratory of Nachmansohn, demonstrated the ability of hydroxylamine to reactivate cholinesterase inhibited by organophosphates. Finally Wilson and Ginsburg using 2-methyl-pyridine as a starting point synthesized the first pyridinium aldoxime reactivator of clinical relevance, pralidoxime (1955).
authors.affiliation: Herbert Wertheim College of Medicine, Florida International University, Department of Cellular Biology & Pharmacology, University Park (11200 SW 8th Street), Miami, 33199 FL, USA. georg.petroianu@fiu.edu
authors.forename: G A
authors.initials: GA
authors.lastname: Petroianu
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000506:poisoning / Q000633:toxicity; D002801:Cholinesterase Reactivators / Q000266:history / Q000494:pharmacology*; D049672:History, 19th Century; D049673:History, 20th Century; D006801:Humans; D019811:Hydroxylamine / Q000737:chemistry / Q000266:history / Q000494:pharmacology*; D010091:Oximes / Q000737:chemistry / Q000266:history / Q000494:pharmacology*; D011220:Pralidoxime Compounds / Q000266:history / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000737:chemistry / Q000266:history / Q000494:pharmacology*
chemical_list: D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D019811:Hydroxylamine; D000110:Acetylcholinesterase