Effects of orally-bioavailable short-acting kappa opioid receptor-selective antagonist LY2456302 on nicotine withdrawal in mice

@article{Jackson2015EffectsOO,
  title={Effects of orally-bioavailable short-acting kappa opioid receptor-selective antagonist LY2456302 on nicotine withdrawal in mice},
  author={Kia J. Jackson and Asti B. Jackson and F. Ivy Carroll and Mohamad Imad Damaj},
  journal={Neuropharmacology},
  year={2015},
  volume={97},
  pages={270-274}
}
View on Elsevier
europepmc.org
23 Citations
Highly Influential Citations
3
Background Citations
9
Results Citations
1

Figures and Tables from this paper

23 Citations

Citation Type

Citation Type

Design and Synthesis of a Novel and Selective Kappa Opioid Receptor (KOR) Antagonist (BTRX-335140).
TLDR
Orally administered CYM-53093 showed robust efficacy in antagonizing KOR agonist-induced prolactin secretion and in tail-flick analgesia in mice and exhibited a broad selectivity over a panel of off-target proteins.
Two short-acting kappa opioid receptor antagonists (zyklophin and LY2444296) exhibited different behavioral effects from the long-acting antagonist norbinaltorphimine in mouse anxiety tests
Itching-like behavior: A common effect of the kappa opioid receptor antagonist 5′-guanidinonaltrindole and the biased kappa opioid receptor agonist 6′-guanidinonaltrindole in mice
Selective kappa opioid antagonists for treatment of addiction, are we there yet?
Analysis of natural product regulation of opioid receptors in the treatment of human disease.
The kappa opioid receptor antagonist aticaprant reverses behavioral effects from unpredictable chronic mild stress in male mice.
TLDR
The results of this study support further study of the role of KORs in regulating circuits related to reward, self-care, and cognition when they are disrupted by chronic stress and are consistent with the clinical development of aticaprant as a therapeutic for stress-related disorders targeted at anhedonia.
Repeated nicotine exposure modulates prodynorphin and pronociceptin levels in the reward pathway.
Fluorine-18-Labeled Antagonist for PET Imaging of Kappa Opioid Receptors.
TLDR
The synthesis of a first 18F-labeled KOR antagonist radiotracer is reported and the initial PET imaging study in a nonhuman primate is conducted.
Neuropeptide systems and new treatments for nicotine addiction
TLDR
Drugs that target neuropeptide systems might decrease the euphoric effects of smoking and improve relapse rates by diminishing withdrawal symptoms and improving stress resilience.
Targeting opioid dysregulation in depression for the development of novel therapeutics.
...
...

References

SHOWING 1-10 OF 51 REFERENCES
Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist.
TLDR
JDTic is the first potent kappa-selective opioid receptor antagonist not derived from an opiate class of compounds and fails to antagonize the analgesic effects of the selective MOP mu-opioid receptor agonists.
Pharmacological properties of JDTic: a novel κ-opioid receptor antagonist
LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders
Effect of the selective kappa-opioid receptor antagonist JDTic on nicotine antinociception, reward, and withdrawal in the mouse
TLDR
The findings clearly show that the KOR is involved in mediating the withdrawal aspects of nicotine dependence, and suggest that blockade of the K OR by selective KOR antagonists may be useful smoking cessation pharmacotherapies.
Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats
TLDR
Depression and stress are two states during cocaine abstinence which users identify as precipitating relapse, and JDTic may have properties which attenuate both.
Development of κ opioid receptor antagonists.
TLDR
The preclinical research conducted in the development of several different classes of selective KOR antagonists are described, a summary of the clinical studies conducted thus far, and recommendations for the type of work needed in the future to determine if these agents would be useful as pharmacotherapies for neuropsychiatric illness are provided.
Pharmacological Evidence for a Motivational Role of κ-Opioid Systems in Ethanol Dependence
TLDR
The results with nor-BNI confirm that κ-opioid receptor antagonism selectively decreases dependence-induced ethanol self-administration, which supports the hypothesis that dynorphin/κ-opIOid systems are dysregulated in dependence and contribute to the increased drinking seen during acute withdrawal in dependent animals.
Long-acting κ opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in mice and lipophilicity
TLDR
The very slow elimination of JDTic from brain is surprising given that it undergoes active efflux, has modest affinity for homogenate, and has a shorter duration of action than nor-BNI under these conditions, and it is proposed that this persistence may result from entrapment in cellular compartments such as lysosomes.
Effects of the kappa opioid receptor antagonist, norbinaltorphimine, on stress and drug-induced reinstatement of nicotine-conditioned place preference in mice
TLDR
Overall, the kappa opioid system may serve as a therapeutic target for suppressing multiple signaling processes which contribute to maintenance of smoking, smoking relapse, and drug abuse in general.
Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence.
  • B. Walker, G. Koob
  • Medicine, Biology
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 2008
TLDR
The results with nor-BNI confirm that kappa-opioid receptor antagonism selectively decreases dependence-induced ethanol self-administration, which supports the hypothesis that dynorphin/kappa-OPioid systems are dysregulated in dependence and contribute to the increased drinking seen during acute withdrawal in dependent rats.
...
...