title: Effects of oximes on rate of decarbamylation of human red blood cell AChE measured with two different methods.
abstract: Treatment regimen of poisonings by organophosphorus (OP) compounds usually includes oxime therapy. The treatment options in soman poisoning are very limited due to rapid aging of the inhibited acetylcholinesterase (AChE), when the enzyme species is considered as irreversibly inhibited and resistant towards reactivation by oximes. Hence, oxime treatment probably comes too late in realistic scenarios. As an alternative, protecting part of the enzyme by reversible inhibition prior to soman exposure has been proposed. One means of protecting against soman poisoning is the prophylactic use of certain reversible inhibitors (carbamates) of AChE. The question whether there is a possibility of an interaction between pre-treating carbamates and oximes at AChE arises. Therefore we studied the effects of the oximes obidoxime, HI 6 and MMB-4 on the rate of decarbamylation for physostigmine- and pyridostigmine-inhibited human erythrocyte AChE both in a dynamically working in vitro model and a static cuvette system. Our results show that HI 6 increased the rate of decarbamylation for both physostigmine- and pyridostigmine-inhibited enzyme in both systems, the observed effect by HI 6 increasing with higher doses. Obidoxime had a slightly accelerating effect on the pyridostigmine-inhibited enzyme. MMB-4 applied to pyridostigmine-inhibited AChE in the static system only showed no difference to the experiments made in absence of oxime. No oxime showed a tendency to retard the rate of decarbamylation.
authors.affiliation: Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-University of Munich, Goethestrasse 33, D-80336 Munich, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Eckert
authors.forename: Peter
authors.initials: P
authors.lastname: Eyer
authors.forename: Marco
authors.initials: M
authors.lastname: Melzer
authors.forename: H
authors.initials: H
authors.lastname: Thiermann
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002219:Carbamates / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D010091:Oximes / Q000494:pharmacology*
chemical_list: D002219:Carbamates; D010091:Oximes; D000110:Acetylcholinesterase