PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 25646463-1 2015 Ongoing mouse studies of a proposed therapy for cocaine abuse based on viral gene transfer of butyrylcholinesterase (BChE) mutated for accelerated cocaine hydrolysis have yielded surprising effects on aggression. Cocaine 48-55 butyrylcholinesterase Mus musculus 94-115 25814464-3 2015 For months or years, gene transfer of a BChE mutated into a cocaine hydrolase (CocH) can maintain enzyme levels that destroy cocaine within seconds after appearance in the blood stream, allowing little to reach the brain. Cocaine 60-67 butyrylcholinesterase Mus musculus 40-44 25646463-1 2015 Ongoing mouse studies of a proposed therapy for cocaine abuse based on viral gene transfer of butyrylcholinesterase (BChE) mutated for accelerated cocaine hydrolysis have yielded surprising effects on aggression. Cocaine 48-55 butyrylcholinesterase Mus musculus 117-121 23849058-4 2013 We recently designed and discovered a BChE mutant (A199S/F227A/S287G/A328W/Y332G) with a high catalytic activity (kcat=5700 min-1, Km=3.1 muM) specifically for cocaine, and the mutant was proven effective in protecting mice from acute cocaine toxicity of a lethal dose of cocaine (180 mg/kg of body weight, LD100). Cocaine 160-167 butyrylcholinesterase Mus musculus 38-42 23849058-4 2013 We recently designed and discovered a BChE mutant (A199S/F227A/S287G/A328W/Y332G) with a high catalytic activity (kcat=5700 min-1, Km=3.1 muM) specifically for cocaine, and the mutant was proven effective in protecting mice from acute cocaine toxicity of a lethal dose of cocaine (180 mg/kg of body weight, LD100). Cocaine 235-242 butyrylcholinesterase Mus musculus 38-42 23849058-9 2013 In particular, it has been demonstrated that the BChE mutant (administered to mice 1 min prior to cocaine) can quickly metabolize cocaine and completely eliminate cocaine-induced hyperactivity in rodents, implying that the BChE mutant may be developed as a promising therapeutic agent for cocaine abuse treatment. Cocaine 98-105 butyrylcholinesterase Mus musculus 49-53 23849058-9 2013 In particular, it has been demonstrated that the BChE mutant (administered to mice 1 min prior to cocaine) can quickly metabolize cocaine and completely eliminate cocaine-induced hyperactivity in rodents, implying that the BChE mutant may be developed as a promising therapeutic agent for cocaine abuse treatment. Cocaine 98-105 butyrylcholinesterase Mus musculus 223-227 23849058-9 2013 In particular, it has been demonstrated that the BChE mutant (administered to mice 1 min prior to cocaine) can quickly metabolize cocaine and completely eliminate cocaine-induced hyperactivity in rodents, implying that the BChE mutant may be developed as a promising therapeutic agent for cocaine abuse treatment. Cocaine 130-137 butyrylcholinesterase Mus musculus 49-53 23849058-9 2013 In particular, it has been demonstrated that the BChE mutant (administered to mice 1 min prior to cocaine) can quickly metabolize cocaine and completely eliminate cocaine-induced hyperactivity in rodents, implying that the BChE mutant may be developed as a promising therapeutic agent for cocaine abuse treatment. Cocaine 130-137 butyrylcholinesterase Mus musculus 223-227 23849058-9 2013 In particular, it has been demonstrated that the BChE mutant (administered to mice 1 min prior to cocaine) can quickly metabolize cocaine and completely eliminate cocaine-induced hyperactivity in rodents, implying that the BChE mutant may be developed as a promising therapeutic agent for cocaine abuse treatment. Cocaine 130-137 butyrylcholinesterase Mus musculus 49-53 23849058-9 2013 In particular, it has been demonstrated that the BChE mutant (administered to mice 1 min prior to cocaine) can quickly metabolize cocaine and completely eliminate cocaine-induced hyperactivity in rodents, implying that the BChE mutant may be developed as a promising therapeutic agent for cocaine abuse treatment. Cocaine 130-137 butyrylcholinesterase Mus musculus 223-227 23849058-9 2013 In particular, it has been demonstrated that the BChE mutant (administered to mice 1 min prior to cocaine) can quickly metabolize cocaine and completely eliminate cocaine-induced hyperactivity in rodents, implying that the BChE mutant may be developed as a promising therapeutic agent for cocaine abuse treatment. Cocaine 130-137 butyrylcholinesterase Mus musculus 49-53 23849058-9 2013 In particular, it has been demonstrated that the BChE mutant (administered to mice 1 min prior to cocaine) can quickly metabolize cocaine and completely eliminate cocaine-induced hyperactivity in rodents, implying that the BChE mutant may be developed as a promising therapeutic agent for cocaine abuse treatment. Cocaine 130-137 butyrylcholinesterase Mus musculus 223-227 12130672-2 2002 Molecular modeling of BChE complexed with cocaine suggested that the inefficient hydrolysis (k(cat) = 4 min(-1)) involves a rotation toward the catalytic triad, hindered by Tyr332. Cocaine 42-49 butyrylcholinesterase Mus musculus 22-26 21540357-0 2011 Prolonged toxic effects after cocaine challenge in butyrylcholinesterase/plasma carboxylesterase double knockout mice: a model for butyrylcholinesterase-deficient humans. Cocaine 30-37 butyrylcholinesterase Mus musculus 51-72 21540357-0 2011 Prolonged toxic effects after cocaine challenge in butyrylcholinesterase/plasma carboxylesterase double knockout mice: a model for butyrylcholinesterase-deficient humans. Cocaine 30-37 butyrylcholinesterase Mus musculus 131-152 21540357-2 2011 One explanation for this observation is that cocaine abusers may posses one or more of the 58 possible known mutations in the butyrylcholinesterase gene (BCHE). Cocaine 45-52 butyrylcholinesterase Mus musculus 126-152 21540357-2 2011 One explanation for this observation is that cocaine abusers may posses one or more of the 58 possible known mutations in the butyrylcholinesterase gene (BCHE). Cocaine 45-52 butyrylcholinesterase Mus musculus 154-158 21540357-11 2011 The carboxylesterase/BChE double knockout mouse model demonstrates the importance of endogenous BChE for protection against cocaine toxicity and provides an in vivo system for studying drug sensitivity of humans who carry a BChE mutation. Cocaine 124-131 butyrylcholinesterase Mus musculus 21-25 21540357-11 2011 The carboxylesterase/BChE double knockout mouse model demonstrates the importance of endogenous BChE for protection against cocaine toxicity and provides an in vivo system for studying drug sensitivity of humans who carry a BChE mutation. Cocaine 124-131 butyrylcholinesterase Mus musculus 96-100 20971807-4 2011 The present study accounting for the mutation-caused changes of the catalytic activities of BChE against both (-)-cocaine and ACh by means of molecular modeling and site-directed mutagenesis has led to identification of three BChE mutants that have not only a considerably improved catalytic efficiency against (-)-cocaine but also the desirable selectivity for (-)-cocaine over ACh. Cocaine 110-121 butyrylcholinesterase Mus musculus 92-96 20971807-4 2011 The present study accounting for the mutation-caused changes of the catalytic activities of BChE against both (-)-cocaine and ACh by means of molecular modeling and site-directed mutagenesis has led to identification of three BChE mutants that have not only a considerably improved catalytic efficiency against (-)-cocaine but also the desirable selectivity for (-)-cocaine over ACh. Cocaine 110-121 butyrylcholinesterase Mus musculus 226-230 20971807-4 2011 The present study accounting for the mutation-caused changes of the catalytic activities of BChE against both (-)-cocaine and ACh by means of molecular modeling and site-directed mutagenesis has led to identification of three BChE mutants that have not only a considerably improved catalytic efficiency against (-)-cocaine but also the desirable selectivity for (-)-cocaine over ACh. Cocaine 311-322 butyrylcholinesterase Mus musculus 92-96 20971807-4 2011 The present study accounting for the mutation-caused changes of the catalytic activities of BChE against both (-)-cocaine and ACh by means of molecular modeling and site-directed mutagenesis has led to identification of three BChE mutants that have not only a considerably improved catalytic efficiency against (-)-cocaine but also the desirable selectivity for (-)-cocaine over ACh. Cocaine 311-322 butyrylcholinesterase Mus musculus 226-230 20971807-4 2011 The present study accounting for the mutation-caused changes of the catalytic activities of BChE against both (-)-cocaine and ACh by means of molecular modeling and site-directed mutagenesis has led to identification of three BChE mutants that have not only a considerably improved catalytic efficiency against (-)-cocaine but also the desirable selectivity for (-)-cocaine over ACh. Cocaine 311-322 butyrylcholinesterase Mus musculus 92-96 20971807-4 2011 The present study accounting for the mutation-caused changes of the catalytic activities of BChE against both (-)-cocaine and ACh by means of molecular modeling and site-directed mutagenesis has led to identification of three BChE mutants that have not only a considerably improved catalytic efficiency against (-)-cocaine but also the desirable selectivity for (-)-cocaine over ACh. Cocaine 311-322 butyrylcholinesterase Mus musculus 226-230 20971807-5 2011 Two representative BChE mutants have been confirmed to be potent in actual protection of mice from acute toxicity (convulsion and lethality) of a lethal dose of cocaine (180 mg/kg). Cocaine 161-168 butyrylcholinesterase Mus musculus 19-23 20971807-6 2011 Pretreatment with the BChE mutant (i.e., 1 min before cocaine administration) dose-dependently protected mice against cocaine-induced convulsions and lethality. Cocaine 54-61 butyrylcholinesterase Mus musculus 22-26 20971807-6 2011 Pretreatment with the BChE mutant (i.e., 1 min before cocaine administration) dose-dependently protected mice against cocaine-induced convulsions and lethality. Cocaine 118-125 butyrylcholinesterase Mus musculus 22-26 23840704-0 2013 Gene transfer of mutant mouse cholinesterase provides high lifetime expression and reduced cocaine responses with no evident toxicity. Cocaine 91-98 butyrylcholinesterase Mus musculus 30-44 20971807-2 2011 There is a recognized, promising anticocaine medication to accelerate cocaine metabolism, producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway [i.e., cocaine hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma]. Cocaine 37-44 butyrylcholinesterase Mus musculus 237-258 20971807-2 2011 There is a recognized, promising anticocaine medication to accelerate cocaine metabolism, producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway [i.e., cocaine hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma]. Cocaine 37-44 butyrylcholinesterase Mus musculus 260-264 20971807-2 2011 There is a recognized, promising anticocaine medication to accelerate cocaine metabolism, producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway [i.e., cocaine hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma]. Cocaine 70-77 butyrylcholinesterase Mus musculus 237-258 20971807-2 2011 There is a recognized, promising anticocaine medication to accelerate cocaine metabolism, producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway [i.e., cocaine hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma]. Cocaine 70-77 butyrylcholinesterase Mus musculus 260-264 19416087-4 2009 The importance of BChE in detoxication of cocaine has been demonstrated by hepatotoxicity and cardiotoxicity in cocaine-challenged BChE KO mice. Cocaine 42-49 butyrylcholinesterase Mus musculus 18-22 19416087-4 2009 The importance of BChE in detoxication of cocaine has been demonstrated by hepatotoxicity and cardiotoxicity in cocaine-challenged BChE KO mice. Cocaine 42-49 butyrylcholinesterase Mus musculus 131-135 19416087-4 2009 The importance of BChE in detoxication of cocaine has been demonstrated by hepatotoxicity and cardiotoxicity in cocaine-challenged BChE KO mice. Cocaine 112-119 butyrylcholinesterase Mus musculus 18-22 19416087-4 2009 The importance of BChE in detoxication of cocaine has been demonstrated by hepatotoxicity and cardiotoxicity in cocaine-challenged BChE KO mice. Cocaine 112-119 butyrylcholinesterase Mus musculus 131-135 19067679-1 2008 In mice, cocaine is detoxified to inactive products by butyrylcholinesterase (BChE) and carboxylesterase. Cocaine 9-16 butyrylcholinesterase Mus musculus 55-76 19067679-1 2008 In mice, cocaine is detoxified to inactive products by butyrylcholinesterase (BChE) and carboxylesterase. Cocaine 9-16 butyrylcholinesterase Mus musculus 78-82 19067679-3 2008 The focus of this investigation was to elucidate the importance of BChE in reducing pathophysiological effects following cocaine exposure. Cocaine 121-128 butyrylcholinesterase Mus musculus 67-71 19067679-4 2008 Previous studies examining the effects of cocaine on BChE deficient animals relied on chemical inhibition of BChE with tetraisopropyl pyrophosphoramide (iso-OMPA). Cocaine 42-49 butyrylcholinesterase Mus musculus 53-57 19067679-5 2008 The creation of the BChE knockout mouse has provided a model for studying pathological effects of cocaine in mice free of chemical confounders. Cocaine 98-105 butyrylcholinesterase Mus musculus 20-24 19067679-6 2008 We hypothesized that mice with low or no BChE activity would have reduced cocaine metabolism, leading to hepatotoxicity and cardiomyopathy. Cocaine 74-81 butyrylcholinesterase Mus musculus 41-45 19067679-12 2008 The observed functional changes following acute high-dose and chronic low-dose cocaine in BChE-/- and +/- mice warrants further investigation into the possibility of increased cocaine toxicity in human beings with BChE deficiency. Cocaine 79-86 butyrylcholinesterase Mus musculus 90-94 19067679-12 2008 The observed functional changes following acute high-dose and chronic low-dose cocaine in BChE-/- and +/- mice warrants further investigation into the possibility of increased cocaine toxicity in human beings with BChE deficiency. Cocaine 176-183 butyrylcholinesterase Mus musculus 90-94 12130672-4 2002 The resulting mutant BChE reduced cocaine burden in tissues, accelerated plasma clearance by 20-fold, and prevented cocaine-induced hyperactivity in mice. Cocaine 34-41 butyrylcholinesterase Mus musculus 21-25 12130672-4 2002 The resulting mutant BChE reduced cocaine burden in tissues, accelerated plasma clearance by 20-fold, and prevented cocaine-induced hyperactivity in mice. Cocaine 116-123 butyrylcholinesterase Mus musculus 21-25 9865234-2 1998 Exogenously enhanced plasma cholinesterase activity is protective against cocaine toxicity in animals. Cocaine 74-81 butyrylcholinesterase Mus musculus 28-42 12019200-0 2002 Characterization of butyrylcholinesterase antagonism of cocaine-induced hyperactivity. Cocaine 56-63 butyrylcholinesterase Mus musculus 20-41 12019200-1 2002 Although there are several published demonstrations that exogenous butyrylcholinesterase (EC 3.1.1.8) works to antagonize cocaine in vivo, a systematic characterization of the enzyme-drug interaction is lacking as is confirmation of the mechanism of effect. Cocaine 122-129 butyrylcholinesterase Mus musculus 67-88 9865234-3 1998 Cocaine users tend to have lower plasma cholinesterase activity than controls. Cocaine 0-7 butyrylcholinesterase Mus musculus 40-54 9865234-4 1998 Yet, when cocaine users are allowed to use cocaine in controlled settings without dietary restriction, their plasma cholinesterase activity increases. Cocaine 10-17 butyrylcholinesterase Mus musculus 116-130 1432697-0 1992 Decreased plasma cholinesterase activity enhances cocaine toxicity in mice. Cocaine 50-57 butyrylcholinesterase Mus musculus 17-31 2263658-2 1990 Cocaine can be hydrolyzed by serum cholinesterase (ChE) to inactive products, or be oxidized by hepatic cytochrome P-450 and FAD-containing monooxygenase (FADM). Cocaine 0-7 butyrylcholinesterase Mus musculus 35-49 2263658-2 1990 Cocaine can be hydrolyzed by serum cholinesterase (ChE) to inactive products, or be oxidized by hepatic cytochrome P-450 and FAD-containing monooxygenase (FADM). Cocaine 0-7 butyrylcholinesterase Mus musculus 51-54 32387315-4 2020 In particular, rational design and site-directed mutagenesis transformed human serum recombinant butyrylcholinesterase (BChE) into a highly efficient cocaine hydrolase with drastically improved catalytic efficiency toward (-)-cocaine. Cocaine 150-157 butyrylcholinesterase Mus musculus 120-124 32387315-4 2020 In particular, rational design and site-directed mutagenesis transformed human serum recombinant butyrylcholinesterase (BChE) into a highly efficient cocaine hydrolase with drastically improved catalytic efficiency toward (-)-cocaine. Cocaine 226-233 butyrylcholinesterase Mus musculus 120-124