title: Is rivastigmine safe as pretreatment against nerve agents poisoning? A pharmacological, physiological and cognitive assessment in healthy young adult volunteers.
abstract: Rivastigmine, a reversible cholinesterase inhibitor, approved as a remedy in Alzheimer's disease, was suggested as pretreatment against nerve agents poisoning. We evaluated the pharmacokinetic, pharmacodynamic, physiologic, cognitive and emotional effects of repeated rivastigmine in young healthy male adults, in a double blind, placebo controlled crossover trial. Three groups completed 3 treatment periods: 0, 1.5 and 3mg twice a day, for a total of 5 intakes. Parameters monitored were: vital signs, ECG, laboratory tests, sialometry, visual accommodation, inspiratory peak flow, and cognitive function tests. Adverse reactions were mild. Peak blood levels and peak cholinesterase inhibition increased with repeated intakes, and high variability and non-linear pharmacokinetics were demonstrated. In addition, two cognitive functions were affected (perceptual speed and dynamic tracking). The complicated pharmacological profile and the high inter-personal variability limit the potential use of rivastigmine as pretreatment for war fighters and first responders.
authors.affiliation: Israel Defense Force, Medical Corps, Ramat Gan, Israel; Clinical Pharmacology and Toxicology Unit, Carmel Medical Center, Haifa, Israel; The Rappaport Family Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address: ophir.lavon@clalit.org.il.
authors.forename: Ophir
authors.initials: O
authors.lastname: Lavon
authors.affiliation: Israel Defense Force, Medical Corps, Ramat Gan, Israel; Israel Ministry of Defense, Israel; The Institute for Research in Military Medicine, The Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
authors.forename: Arik
authors.initials: A
authors.lastname: Eisenkraft
authors.affiliation: Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Blanca
authors.affiliation: Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Lily
authors.initials: L
authors.lastname: Raveh
authors.affiliation: Israel Defense Force, Medical Corps, Ramat Gan, Israel.
authors.forename: Erez
authors.initials: E
authors.lastname: Ramaty
authors.affiliation: Israel Defense Force, Medical Corps, Ramat Gan, Israel; Geha Mental Health Center, Petach-Tikva, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Krivoy
authors.affiliation: Clinical Research Center, Tel-Aviv Medical Center, Tel-Aviv, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Atsmon
authors.affiliation: Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Ettie
authors.initials: E
authors.lastname: Grauer
authors.affiliation: Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Brandeis
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects; D005500:Follow-Up Studies; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000097:blood* / Q000494:pharmacology*; D000068836:Rivastigmine / Q000097:blood* / Q000494:pharmacology*; D012463:Saliva / Q000378:metabolism; D013997:Time Factors; D014785:Vision, Ocular / Q000187:drug effects; D014792:Visual Acuity / Q000187:drug effects; D055815:Young Adult
chemical_list: D018696:Neuroprotective Agents; D000110:Acetylcholinesterase; D000068836:Rivastigmine
keywords: Cholinesterase inhibitors; Nerve agents; Organophosphates; Psychometric evaluation; Rivastigmine