Plasma butyrylcholinesterase activity and cocaine half-life differ significantly in rhesus and squirrel monkeys

Carmona, Gilberto N.; Baum, Ira; Schindler, Charles W.; Goldberg, Steven R.; Jufer, Rebecca A.; Cone, Edward J.; Slaughter, Elizabeth; Belendiuk, George; Gorelick, David A.

doi:10.1016/0024-3205(96)00392-x

Cited by 22 publications

(12 citation statements)

References 15 publications

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“…Thus, any change in the activity of BChE might be expected to change the levels of cocaine in the body. Carmona et al showed that rhesus monkeys differ from squirrel monkeys in their endogenous levels of BChE and that these different levels of BChE were associated with differences in the speed of cocaine metabolism in plasma between the two species [18]. Thus, differences in BChE plasma levels can alter the blood levels of cocaine, which, in turn, could alter any effect related to body levels of cocaine.…”

mentioning

confidence: 99%

Accelerating Cocaine Metabolism as an Approach to the Treatment of Cocaine Abuse and Toxicity

Schindler

Goldberg

2012

Future Med. Chem.

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One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans.

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confidence: 99%

Accelerating Cocaine Metabolism as an Approach to the Treatment of Cocaine Abuse and Toxicity

Schindler

Goldberg

2012

Future Med. Chem.

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“…[6][7][8][9] ChE can be used as an index of cholinergic function and changes in enzyme activity may indicate alterations in the availability of acetylcholine at the receptor level. [10][11][12][13][14] In vivo, ChE activity reflecting the functional quantities of the enzyme can be assessed using blood, plasma, and red blood cells. Inhibition of ChE leads to a down-regulation of cholinergic receptors.…”

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confidence: 99%

Spectrophotometric Determination of Plasma and Red Blood Cell Cholinesterase Activity of 53 Fruit Farm Workers Pre- and Post-Exposed Chlorpyrifos for One Fruit Crop

Thetkathuek

Keifer²,

Fungladda

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Chlorpyrifos (O,O-diethyl 0-(3,5,6-trichloro-2-pyridyl) phosphorothioate) belongs to the organophosphate insecticide (OPs) family, and is widely used to kill aphids in fruit farms. The demand for this insecticide is increasing. To our knowledge, there is no biological monitoring data for fruitfarm worker exposure to chlorpyrifos insecticide is available in Thailand. Biological monitoring is an essential component of any comprehensive assessment of exposure. In fact, these farm workers were at high risk of direct exposure to pesticides while mixing, loading, or spraying pesticide. [1][2][3][4] It has been reported that chlorpyrifos insecticide is rapidly absorbed by skin contact and/or oral administration, metabolized and excreted by mammals.5) The primary mechanism of action of organophosphorus (OP) insecticides like chlorpyrifos involves the inhibition of acetylcholinesterase (AChE), resulting in a wide range of neurotoxic effects in humans, such as sensory and motor neuropathy with permanent paralysis. The inhibition of cholinesterase enzyme (ChE) may cause acetylcholine accumulation at the synaptic cleft, causing the stimulation of autonomic receptors and depolarizing blocks of neuromuscular junction receptors in the human body. In addition, it was proposed that both long-term exposure to subclinical doses of OP, and after acute intoxication, could be responsible for chronic OP-induced neuropsychiatric disorders. [6][7][8][9] ChE can be used as an index of cholinergic function and changes in enzyme activity may indicate alterations in the availability of acetylcholine at the receptor level. [10][11][12][13][14] In vivo, ChE activity reflecting the functional quantities of the enzyme can be assessed using blood, plasma, and red blood cells. Inhibition of ChE leads to a down-regulation of cholinergic receptors. The levels of ChE appear to be controlled by the interaction of acetylcholine with its receptors, with enhanced interaction increasing the levels of ChE. 15)This study aims to investigate any changes in ChE activity reflecting the cholinergic function of fruit farm workers exposed to the neurotoxin, chlorpyrifos insecticide, during one fruit crop. For this purpose, the blood ChE activities of 53 farm workers on fruit farms in Rayong Province, Thailand, were collected and analyzed.In the present study, a significant decrease in plasma (PChE), but not red blood cell ChE (AChE) activity after exposure to chlorpyrifos in the spraying season, compared with the non-spraying season, was found. The results suggest an interaction between chlorpyrifos and monoaminergic-cholinergic neurotransmission that leads to a decrease in the functional enzyme available to degrade acetylcholine. We propose that PChE activity can be used as a biomarker for monitoring early toxicity induced by chlorpyrifos insecticide. Determination of baseline red blood cell and plasma cholinesterase activity among applicators in the non-spraying season is very important, before identifying the effects of these pesticide exposures. Experiment...

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“…The presence of significant levels of circulating BChE in rhesus macaques (Carmona et al, 1996) seems to suggest that active removal of primate cholinesterase in this animal system is restricted to AChE. However, primate BChE may also be actively and effectively eHminated from the circulation at rates similar to those of AChE, while its apparent prevalence in the circulation may be a reflection of its high tumover rate.…”

Section: Facilitated Elimination Of Cholinesterases From the Circulatmentioning

confidence: 97%

Generation of Recombinant Human Ache Op-Scavengers With Extended Circulatory Longevity

Shafferman¹

2004

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of infomation. Send co.mments regarding this burden estimate or any other aspect of this colledion of information, including suggestions for reducing this burden to Washington Headquarters Sen/ices, Directorate Ibr Infbmialion Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Papenvork Reduction Project (0704-01881, Washington, DC 20503 Agency Use Only (Leave blank). 11. Supplementary Notes (i.e., report contains color photos, report contains appendix in non-print form, etc.)Original contains color plates: All DTIC reproductions will be in black and white. 12a. Distribution/Availability Statement)Approved for public release; distribution unlimited Abstract {Maximum 200 Words) 12b. Distribution Code (Leave Blank)The use of recombinant human acetylcholinesterase as an effective bioscavenger of organophosphorus compounds requires that it reside in the circulation for sufficiently long periods of time. We have demonstrated in the past that extension of the circulatory lifetime of AChE can be achieved either by optimizing post-translation-related enzyme processing or by chemical conjugation of polyethylene glycol (PEG) moieties to the enzyme. To delineate the interrelationship between these two modes of AChE modulation with regard to pharmacokinetic behavior, an array of AChE molecules differing in their post-translation-related processing was subjected to PEG-conjugation and monitored for their pharmacokinetic performance. In all cases tested to date, PEG-conjugation was found to give rise to enzyme species which reside for very long periods of time in the circulation of mice in a nearly equal manner. We have now found a novel mode of AChE circulatory elimination based on the recognition of specific amino acid-related epitopes. This unique clearance mechanism can also be efficiently overcome by enzyme PEGylation. These findings indicate that the circulatory residence is dictated primarily by the PEG appendage, and that cost-effective microorganisms-based production systems which do not support animal-cell-related enzyme processing, may be utilized for large-scale AChE production. In line with this notion, we have constructed a synthetic human AChE gene designed for optimal expression in microorganism-based production systems, which will now be tested for its ability to sustain human AChE production.14. Subject Terms (keywords previously assigned to proposal abstract or terms which apply to this award) I. GENERAL INTRODUCTIONThe primary role of acetylcholinesterase (acetylcholine acetylhydrolase 3.1.1.7, AChE) is the termination of impulse transmission in cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylchoUne (ACh). The enzyme has been th...

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Plasma butyrylcholinesterase activity and cocaine half-life differ significantly in rhesus and squirrel monkeys

Cited by 22 publications

References 15 publications

Accelerating Cocaine Metabolism as an Approach to the Treatment of Cocaine Abuse and Toxicity

Accelerating Cocaine Metabolism as an Approach to the Treatment of Cocaine Abuse and Toxicity

Spectrophotometric Determination of Plasma and Red Blood Cell Cholinesterase Activity of 53 Fruit Farm Workers Pre- and Post-Exposed Chlorpyrifos for One Fruit Crop

Generation of Recombinant Human Ache Op-Scavengers With Extended Circulatory Longevity

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