title: In vitro kinetic interactions of pyridostigmine, physostigmine and soman with erythrocyte and muscle acetylcholinesterase from different species.
abstract: The low effectiveness of atropine and oxime treatment in soman poisoning may be enhanced by carbamates pre-treatment. For ethical reasons medical countermeasures can only be tested in animal models despite the fact of substantial species differences. With this kinetic in vitro study the interactions between pyridostigmine, physostigmine and soman with human, Rhesus monkey, swine and guinea pig erythrocyte AChE were investigated. In addition, the effect of the carbamates on the residual activity and enzyme recovery after soman inhibition was examined with erythrocyte and intercostal muscle AChE from these species with a dynamic in vitro model with real-time determination of AChE activity. Only small to moderate species differences of the inhibition and decarbamylation kinetics were recorded. It was possible to show that with erythrocyte and muscle AChE a similar level of protection by carbamates and reactivation after discontinuation of the carbamates and soman could be observed. Thus, these data indicate that carbamate pre-treatment is expected to protect a critical level of muscle AChE and confirm the presumption that erythrocyte AChE may serve as a surrogate for synaptic AChE. Hence, these and previous data fortify the notion that erythrocyte AChE is a proper tool for in vitro kinetic studies as well as for therapeutic monitoring in experimental and clinical studies.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
authors.forename: N M
authors.initials: NM
authors.lastname: Herkert
authors.forename: H
authors.initials: H
authors.lastname: Thiermann
authors.forename: F
authors.initials: F
authors.lastname: Worek
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D010830:Physostigmine / Q000737:chemistry / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000737:chemistry / Q000494:pharmacology; D012999:Soman / Q000494:pharmacology*; D013045:Species Specificity; D013552:Swine
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D012999:Soman; D010830:Physostigmine; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide