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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., The original document contains color images. Published in Neurotoxicology and Teratology, v34 n3 p323-330, 2012.

Huperzine A is potentially superior to pyridostigmine bromide as a pretreatment for nerve agent intoxication because it inhibits acetylcholinesterase both peripherally and centrally, unlike pyridostigmine, which acts only peripherally. Using rhesus monkeys, we evaluated the time course of acetylcholinesterase and butyrylcholinesterase inhibition following four different doses of -(-)huperzine A: 5, 10, 20, and 40 g/kg. Acetylcholinesterase inhibition peaked 30 min after intramuscular injection and varied dose dependently, ranging from about 30% to 75%. Subsequently, cognitive-behavioral functioning was also evaluated at each dose of huperzine A using a six-item serial-probe recognition task that assessed attention, motivation, and working memory. Huperzine did not impair performance, but physostigmine did. The results demonstrate that huperzine A can selectively and reversibly inhibit acetylcholinesterase without cognitive-behavioral side effects, thus warranting further study., Published in Pharmacology, Biochemistry and Behavior, v94 n3 p477-481, 2010.

Human serum butyrylcholinesterase (Hu BChE) is currently under advanced development as a pretreatment drug for organophosphate (OP) poisoning in humans. Toward this effort, a procedure for the large-scale purification of Hu BChE from Cohn fraction IV-4 was developed, its pharmacokinetic properties were established, its shelf life was evaluated at various temperatures, and its safety and efficacy were examined. It was shown to protect mice, rats, guinea pigs, and monkeys against multiple LD50 challenges of OP nerve agents by i.v. or s.c. bolus injections. Since inhalation is the most likely route of exposure on the battlefield or in public places, the aim of this study was to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to sarin (GB) vapor. The study was conducted in minipigs because the pig offers many similarities in anatomy and physiology to humans. Male G ttingen minipigs were subjected to one of the following treatments: (1) Air exposure; (2) GB vapor exposure; and (3) pretreatment with 7.5 mg/kg of Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection, 24 h prior to whole-body exposure to GB vapor at a concentration of 4.1 mg/m3 for 60 min or 11.4 mg/m3 for 10 min. EEG, ECG, and pupil size were monitored throughout exposure, and blood drawn from a surgically implanted jugular catheter before and throughout the exposure period was analyzed for acetylcholinesterase (AChE) and BChE activities, and the amount of GB present in plasma. Baseline blood AChE and BChE activities were 2.5 0.1 U/ml and 0.14 0.01 U/ml, respectively. Animals pretreated with 7.5 mg/kg of Hu BChE showed peak blood BChE activity of 41.2 0.9 U/ml with a mean residence time of 287 53 h., See also ADA562561. RTO-MP-HFM-181 Human Performance Enhancement for NATO Military Operations (Science, Technology and Ethics) (Amelioration des performances humaines dans les operations militaires de l'OTAN (Science, Technologie et Ethique)). RTO Human Factors and Medicine Panel (HFM) Symposium held in Sofia, Bulgaria, on 5-7 October 2009., The original document contains color images.

Huperzine A is potentially superior to pyridostigmine bromide as a pretreatment for nerve agent intoxication because it inhibits acetylcholinesterase both peripherally and centrally, unlike pyridostigmine, which acts only peripherally. Using rhesus monkeys, we evaluated the time course of acetylcholinesterase and butyrylcholinesterase inhibition following four different doses of -(-)huperzine A: 5, 10, 20, and 40 ug/kg. Acetylcholinesterase inhibition peaked 30 minutes after intramuscular injection and varied dose dependently, ranging from about 30% to 75%. Subsequently, cognitive-behavioral functioning was also evaluated at each dose of huperzine A using a six-item serial-probe recognition task that assessed attention, motivation, and working memory. The results demonstrate that huperzine A can selectively and reversibly inhibit acetylcholinesterase without cognitive-behavioral side effects, thus warranting further study., The original document contains color images.