title: Characterization of human serum butyrylcholinesterase in rhesus monkeys: behavioral and physiological effects.
abstract: The effects of a large dose of human serum butyrylcholinesterase (HuBChE) were evaluated in rhesus monkeys using a serial-probe recognition (SPR) task designed to assess attention and short-term memory. Each monkey received an intravenous injection of 150 mg (105,000 U or 30 mg/kg) of HuBChE 60 min prior to testing on the SPR task. Concurrent with the cognitive-behavioral assessment, blood was collected at various time points throughout the study and was analyzed for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, anti-BChE antibody production and gross clinical pathology (i.e., complete blood count and clinical chemistry panel). HuBChE revealed a peak blood activity of 227 U/ml at 5 min after intravenous injection and a mean residence time of approximately 72 h. No cognitive-behavioral decrements of any kind in SPR performance and no toxic signs in clinical pathology were detected in any of the blood assays during the 5 weeks of observation. Anti-HuBChE antibodies peaked at about 14 days after injection, with no concomitant behavioral changes. These results demonstrate the behavioral and physiological safety of HuBChE in rhesus monkeys and support its development as a bioscavenger for the prophylaxis of chemical warfare agent toxicity in humans.
authors.affiliation: Division of Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA. todd.myers2@us.army.mil
authors.forename: Todd M
authors.initials: TM
authors.lastname: Myers
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Ramachandra S
authors.initials: RS
authors.lastname: Naik
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Clark
authors.forename: Bhupendra P
authors.initials: BP
authors.lastname: Doctor
authors.forename: Ashima
authors.initials: A
authors.lastname: Saxena
mesh_terms: D000818:Animals; D000931:Antidotes / Q000009:adverse effects; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001772:Blood Cell Count; D002091:Butyrylcholinesterase / Q000009:adverse effects / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007275:Injections, Intravenous; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008253:Macaca mulatta
chemical_list: D000931:Antidotes; D007074:Immunoglobulin G; D002091:Butyrylcholinesterase