Experimental Treatments for Cocaine Toxicity: A Difficult Transition to the Bedside

  title={Experimental Treatments for Cocaine Toxicity: A Difficult Transition to the Bedside},
  author={Nicholas J. Connors and Robert S. Hoffman},
  journal={The Journal of Pharmacology and Experimental Therapeutics},
  pages={251 - 257}
  • N. Connors, R. Hoffman
  • Published 1 November 2013
  • Biology
  • The Journal of Pharmacology and Experimental Therapeutics
Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. Although there is no true antidote to cocaine toxicity, current management strategies address the life-threatening systemic effects, namely hyperthermia, vasospasm, and severe hypertension. Clinicians rely on rapid cooling, benzodiazepines, and α-adrenergic antagonists for management, with years of proven benefit. Experimental agents have been developed to more effectively treat acute toxicity… 

Figures from this paper

Clinical Potential of an Enzyme-based Novel Therapy for Cocaine Overdose
It has been demonstrated that an efficient cocaine-metabolizing enzyme developed in previous studies can rapidly reverse the cocaine toxicity whenever the enzyme is given to a living rat, demonstrating promising clinical potential of an enzyme-based novel therapy for cocaine overdose as a successful example in comparison with the commonly used diazepam.
Sub-lethal toxicity and elimination of the cocaine metabolite, benzoylecgonine: a narrative review.
It is proposed that the ideal treatment for cocaine abuse should not only detoxify cocaine itself but also remove or degrade BE, highlighting the necessity of developing effective BE elimination methods for the development of potential clinical treatments and environmental protections.
Reassessing the Future of the Experimental Treatments for Cocaine Addiction: Conventional Pharmacotherapies?
None of these pharmacotherapies have proven to treat cocaine dependency in a complete, safe and practical manner, especially because many of these treatments cause potentially catastrophic side effects and carry major clinical challenges that may prevent a suitable transition to the bedside.
The encouraging outcomes of the present investigation suggest that it is possible to develop a more effective enzyme therapy for cocaine abuse treatment using one of the most promising BChE mutants, such as E12-7 or E20-7.
A single dose of hCocH-Fc was able to accelerate cocaine metabolism in rats even after 20 days and, thus, block cocaine-induced hyperactivity for a long period of time and could allow dosing once every 2-4 weeks, or longer for cocaine addiction treatment in humans.
Fate of systemically administered cocaine in nonhuman primates treated with the dAd5GNE anticocaine vaccine.
It is demonstrated that the dAd5GNE vaccine-mediated redistribution of administered cocaine is not likely to impact the vaccine safety profile and gross and histopathology of major organs found no vaccine- mediated untoward effects.
Developing Treatments for Stimulant Abuse: A Brief Overview.
  • C. Davidson
  • Psychology, Biology
    East Asian archives of psychiatry : official journal of the Hong Kong College of Psychiatrists = Dong Ya jing shen ke xue zhi : Xianggang jing shen ke yi xue yuan qi kan
  • 2016
An overview of recent preclinical and clinical studies of treatment development for stimulant dependence highlights non-drug treatments such as deep brain stimulation and psychosurgery.
Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity.
Metabolic Enzymes of Cocaine Metabolite Benzoylecgonine.
It is demonstrated for the first time that human butyrylcholinesterase (BChE) is actually active against benzoylecgonine, and that a rationally designed BChE mutant can not only more efficiently accelerate cocaine hydrolysis but also significantly hydrolyze benzoyleCgonine in vitro and in vivo.


Use of antipsychotics to treat cocaine toxicity?
The data are insufficient to support the routine use of antipsychotics for the treatment of acute cocaine toxicity in humans, and the authors’ assertion that safety is implied in the setting of cocaine toxicity is disagreed with.
The effect of olanzapine pretreatment on acute cocaine toxicity in mice
In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaineoxicity and appeared to alter the characteristics of seizures due to cocaine.
Therapeutic use of butyrylcholinesterase for cocaine intoxication.
It is suggested that BChE could be an effective and rapid therapy for the treatment of life-threatening cocaine-induced cardiovascular effects in human while clearing the total body burden of cocaine.
A Novel Substituted Piperazine, CM156, Attenuates the Stimulant and Toxic Effects of Cocaine in Mice
Pretreatment of male Swiss-Webster mice with CM156, before administering either a convulsive or locomotor stimulant dose of cocaine, led to a significant attenuation of these acute effects and data indicate that σ receptors can be targeted to alleviate deleterious actions of cocaine.
Efficacy of a therapeutic cocaine vaccine in rodent models
The feasibility of a therapeutic cocaine vaccine for the treatment of cocaine addiction is established, with decreased levels of cocaine measured in the brain of immunized mice only 30 seconds after intravenous administration of cocaine.
Ziprasidone pretreatment attenuates the lethal effects of cocaine in a mouse model.
  • N. Cleveland, C. DeWitt, K. Heard
  • Medicine, Psychology
    Academic emergency medicine : official journal of the Society for Academic Emergency Medicine
  • 2005
Ziprasidone pretreatment decreased lethality in this mouse model of severe cocaine intoxication to provide preliminary animal data on the efficacy of ziprasid one for the treatment of acute cocaine poisoning.
Ziprasidone, diazepam, or the combination for prevention of cocaine toxicity in a mouse model.
Diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone, however, the combination may be more effective for prevention of cocaine-induced seizures.
Amelioration of the Cardiovascular Effects of Cocaine in Rhesus Monkeys by a Long-Acting Mutant Form of Cocaine Esterase
Findings in monkeys provide strong evidence to suggest that highly efficient cocaine esterases, such as DM CocE, can provide a potential therapeutic option for treatment of acute cocaine intoxication in humans.
Mechanism of Cocaine-Induced Hyperthermia in Humans
A randomized, placebo-controlled study to assess the effects of a low, noneuphoric dose of intranasal cocaine on autonomic and behavioral thermoregulation in healthy cocaine-naive volunteers.