Agents in Development for the Management of Cocaine Abuse

@article{Gorelick2012AgentsID,
  title={Agents in Development for the Management of Cocaine Abuse},
  author={David A. Gorelick and Eliot L. Gardner and Zheng-Xiong Xi},
  journal={Drugs},
  year={2012},
  volume={64},
  pages={1547-1573}
}
Cocaine abuse is a serious health problem in many areas of the world, yet there are no proven effective medications for the treatment of cocaine dependence.Preclinical studies suggest that the reinforcing effect of cocaine that promotes its abuse is mediated by blockade of the presynaptic dopamine transporter. This results in increased dopamine activity in the mesolimbic or meso-accumbens dopamine reward system of brain. Development of new medications to treat cocaine dependence has focused on… 

Medication Development for the Treatment of Cocaine Addiction – Progress at Preclinical and Clinical Levels

  • Z. Xi
  • Psychology, Biology
  • 2012
This review article will focus on those medication strategies that are well-studied in experimental animals and are currently under clinical trials for the treatment of addiction or for other diseases, including DAT-based agonist therapy, DA receptor-based antagonist therapy, glutamate- based therapy, GABA-based therapy and endocannabinoid-based Therapy.

Promising medications for cocaine dependence treatment.

In the present review, the current pharmacotherapeutic approaches to the treatment of cocaine dependence are summarized with a focus on the new patents.

DEVELOPMENT OF COCAINE HYDROLASE FOR THERAPEUTIC TREATMENT OF COCAINE ABUSE

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.

Oral administration of methylphenidate blocks the effect of cocaine on uptake at the Drosophila dopamine transporter.

The data suggest that oral consumption of methylphenidate inhibits the Drosophila dopamine transporter for cocaine uptake, and the inhibition is concentration dependent.

Retraction note to: Recent advances for the treatment of cocaine abuse: central nervous system immunopharmacotherapy

The convergence of phage display and immunopharmacotherapy has allowed for an investigation of the efficacy of protein-based therapeutics acting within the CNS on the effects of cocaine in animal models and has uncovered a new tool in the battle against cocaine addiction.

Substituting a long‐acting dopamine uptake inhibitor for cocaine prevents relapse to cocaine seeking

Data indicate that DUI substitution not only leads to extinction of self‐administration behavior but also prevents reinstatement of drug seeking induced by cocaine re‐exposure, suggesting DUI substitution therapy using compounds with low abuse potential may provide an effective treatment for stimulant addiction.

CTDP-32476: A Promising Agonist Therapy for Treatment of Cocaine Addiction

It is suggested that CTDP-32476 is a unique DAT inhibitor that not only could satisfy ‘drug hunger’ through its slow-onset long-lasting DAT inhibitors action, but also render subsequent administration of cocaine ineffectual—thus constituting a novel and unique compound with translational potential as an agonist therapy for treatment of cocaine addiction.

Agonist replacement therapy for cocaine dependence: a translational review.

The translational review suggests that agonist-replacement therapy, especially monoamine releasers, may be effective for managing cocaine dependence.

Role of the Human Laboratory in the Development of Medications for Alcohol and Drug Dependence

Conclusions suggest that methods to screen the safety and possible efficacy of putative treatments in the human laboratory are validated, but that the efficacy of outpatient treatment also involves compliance factors which have not been adequately modeled in human laboratory studies.
...

References

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A review of the effects of dopaminergic agents on humans, animals, and drug-seeking behavior, and its implications for medication development

It is clear that further research on the effects of cocaine in humans and animals will be critical to the medication development effort, and the potential role of high-affinity DA uptake inhibitors for pharmacotherapeutic application to treat cocaine abuse is discussed.

The dopamine transporter and cocaine medication development: drug self-administration in nonhuman primates.

Several cocaine analogs and other dopamine transporter inhibitors, including analogs of GBR 12909 and WIN 35,065-2, have been shown to reduce cocaine self-administration in nonhuman primates, and pharmacokinetic properties that result in slow onset and long duration of action may enhance their effectiveness to reduced cocaine use while limiting their abuse liability.

Behavioral effects of cocaine and dopaminergic strategies for preclinical medication development

DA partial agonists, in particular the D3-selective and the D1-like partial agonist, offer a more encouraging profile for novel anti-cocaine medications, and are often less severe and only observed at doses above those that antagonize the effects of cocaine.

A novel strategy for the treatment of cocaine addiction

GVG significantly attenuated cocaine‐induced increases in neostriatal synaptic DA in the non‐human primate (baboon) brain as assessed by positron emission tomography (PET) and abolished both the expression and acquisition of cocaine‐ induced conditioned place preference (CPP).

A potential role for GABA(B) agonists in the treatment of psychostimulant addiction.

Systematic clinical studies of GABA(B) agonists are needed to determine the extent to which these drugs might serve as tools to promote abstinence in cocaine users seeking treatment for their addiction.

Relationship between subjective effects of cocaine and dopamine transporter occupancy

This is the first demonstration in humans that the doses used by cocaine abusers lead to significant blockade of DAT, and that this blockade is associated with the subjective effects of cocaine.

Imaging studies on the role of dopamine in cocaine reinforcement and addiction in humans

Analysis of the role of dopamine in the reinforcing effects of cocaine and methylphenidate in humans and its involvement in cocaine addiction suggests strategies to enhance DA brain function in ways that mimic physiological DA activity may be of help in overcoming cocaine addiction.

Modulation of intravenous cocaine effects by chronic oral cocaine in humans

Treatment with a cocaine "agonist" – in this case oral cocaine – can modestly attenuate the subjective and physiological responses to cocaine in humans under conditions that are safely tolerated.
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