ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
Long-lasting effects of a PEGylated mutant cocaine esterase (CocE) on the reinforcing and discriminative stimulus effects of cocaine in rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 26 citations in OpenAlex.
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- Effects of access condition on substance use disorder-like phenotypes in male and female rats self-administering MDPV or cocaine.Drug and alcohol dependence · 2024Article
- Effects of access condition on substance use disorder-like phenotypes in male and female rats self-administering MDPV or cocaine.bioRxiv : the preprint server for biology · 2024Article
- Long-lasting blocking of interoceptive effects of cocaine by a highly efficient cocaine hydrolase in rats.Scientific reports · 2024Article
- 3,4-Methylenedioxypyrovalerone High-Responder Phenotype as a Tool to Evaluate Candidate Medications for Stimulant Use Disorder.The Journal of pharmacology and experimental therapeutics · 2023Article
- Influence of Contingent and Noncontingent Drug Histories on the Development of High Levels of MDPV Self-Administration.The Journal of pharmacology and experimental therapeutics · 2021Article
- Clinical potential of a rationally engineered enzyme for treatment of cocaine dependence: Long-lasting blocking of the psychostimulant, discriminative stimulus, and reinforcing effects of cocaine.Neuropharmacology · 2020Article
- Cebranopadol reduces cocaine self-administration in male rats: Dose, treatment and safety consideration.Neuropharmacology · 2020Article
- Preclinical Evaluation of Vaccines to Treat Opioid Use Disorders: How Close are We to a Clinically Viable Therapeutic?CNS drugs · 2020Review
- Efficient Cocaine Degradation by Cocaine Esterase-Loaded Red Blood Cells.Frontiers in physiology · 2020Article
- Development of Fc-Fused Cocaine Hydrolase for Cocaine Addiction Treatment: Catalytic and Pharmacokinetic Properties.The AAPS journal · 2018Article
- Individual Differences in the Relative Reinforcing Effects of 3,4-Methylenedioxypyrovalerone under Fixed and Progressive Ratio Schedules of Reinforcement in Rats.The Journal of pharmacology and experimental therapeutics · 2017Article
- Biologics to treat substance use disorders: Current status and new directions.Human vaccines & immunotherapeutics · 2016Review
- Determinants of conditioned reinforcing effectiveness: Dopamine D2-like receptor agonist-stimulated responding for cocaine-associated stimuli.European journal of pharmacology · 2015Article
- Differential Roles for Dopamine D1-Like and D2-Like Receptors in Mediating the Reinforcing Effects of Cocaine: Convergent Evidence from Pharmacological and Genetic Studies.Journal of alcoholism and drug dependence · 2015Article
- Medications Discovery: Importance of Assessment of Drug Self Administration Dose-Effect Curves.Journal of alcoholism and drug dependence · 2015Article
- Rational design, preparation, and characterization of a therapeutic enzyme mutant with improved stability and function for cocaine detoxification.ACS chemical biology · 2014Article
- Maintenance of reinforcement to address the chronic nature of drug addiction.Preventive medicine · 2012Article
- Repeated administration of a mutant cocaine esterase: effects on plasma cocaine levels, cocaine-induced cardiovascular activity, and immune responses in rhesus monkeys.The Journal of pharmacology and experimental therapeutics · 2012Article
- Thinking outside the synapse: pharmacokinetic-based medications for cocaine addiction.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Article
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Funding
Abstract
Recent mutagenesis studies have identified a mutant G4C/S10C/T172R/G173Q cocaine esterase (CCRQ CocE) with an in vitro duration of action of >40 days. Although the in vivo duration of CCRQ CocE's action was <24 h, modification of this enzyme with polyethylene glycol (PEG) polymers resulted in a CocE (PEG-CCRQ CocE) capable of preventing cocaine-induced lethality for up to 72 h. The current studies were aimed at providing a detailed characterization of the effectiveness, selectivity, and duration of PEG-CCRQ CocE's actions in cocaine self-administration and discrimination assays in rats. Pretreatment with PEG-CCRQ CocE produced dose-dependent rightward shifts in the dose-response curves for cocaine self-administration and discrimination, with the highest dose of PEG-CCRQ CocE capable of producing an initial shift of cocaine's reinforcing and interoceptive effects of >30-fold to the right, with significant inhibition of these effects observed for up to 72 h. Although PEG-CCRQ CocE also produced slight reductions in the rates of methylphenidate- and food-reinforced responding, these effects were short-lived, lasting <24 h. Finally, when taken together with the finding that PEG-CCRQ CocE failed to alter the cocaine-like interoceptive effects of either methylphenidate or d-amphetamine, these results suggest that PEG-CCRQ CocE possesses a high degree of pharmacologic specificity for cocaine and a prolonged in vivo duration of action. In conclusion, these studies provide strong evidence to support the further development of long-lasting, highly efficient CocEs, such as PEG-CCRQ CocE, as a potential therapeutic option for the treatment of cocaine abuse in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.