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dc.contributor.authorSchindler, Charles W.
dc.contributor.authorJustinova, Zuzana
dc.contributor.authorLafleur, David
dc.contributor.authorWoods, Doug
dc.contributor.authorRoschke, Viktor
dc.contributor.authorSklair-Tavron, Liora
dc.contributor.authorRedhi, Godfrey H.
dc.contributor.authorYasar, Sevil
dc.contributor.authorBergman, Jack
dc.contributor.authorGoldberg, Steven R.
dc.date.accessioned2018-08-27T09:49:22Z
dc.date.available2018-08-27T09:49:22Z
dc.date.issued2012-01-20
dc.identifier.urihttps://dspace.alquds.edu/handle/20.500.12213/791
dc.description.abstractAlthough substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu- CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu-CocH was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000- fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic studies showed that Albu-CocH (5 mg/kg) had a half-life of 56.6 hours in squirrel monkeys. In these studies, plasma levels of cocaine following i.v. 1 mg/kg cocaine were reduced two hours after administration of Albu-CocH, whereas plasma levels of the cocaine metabolite ecgonine methyl ester were increased. These effects were still evident 72 hrs following Albu-CocH administration. In behavioral experiments in monkeys, pretreatment with 5 mg/kg Albu-CocH dramatically decreased self-administration of a reinforcing dose of i.v. cocaine (30 μg/kg/ injection) for over 24 hours. Pretreatment with 5 mg/kg Albu-CocH also attenuated the reinstatement of extinguished cocaine self-administration by an i.v. priming injection of cocaine (0.1 or 0.3 mg/kg) and, in separate studies, attenuated the discriminative stimulus effects of cocaine. The ability of Albu-CocH to attenuate the abuse-related effects of cocaine in squirrel monkeys indicates that further investigation of BChE mutants as potential treatment for cocaine abuse and toxicity is warranted.en_US
dc.description.sponsorshipThis research was supported in part by the Intramural Research Program of the NIH, National Institute on Drug Abuse.en_US
dc.language.isoen_USen_US
dc.subjectcocaineen_US
dc.subjecthydrolaseen_US
dc.subjectself-administrationen_US
dc.subjectreinstatementen_US
dc.subjectdiscriminationen_US
dc.subjectsquirrel monkeysen_US
dc.titleModification of pharmacokinetic and abuse-related effects of cocaine by human-derived cocaine hydrolase in monkeysen_US
dc.typeArticleen_US


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