scholarly journals Pharmacodynamic Relationships between Duration of Action of JDTic-like Kappa-Opioid Receptor Antagonists and Their Brain and Plasma Pharmacokinetics in Rats

2016 ◽  
Vol 7 (12) ◽  
pp. 1737-1745 ◽  
Author(s):  
S. Michael Owens ◽  
Gerald T. Pollard ◽  
James L. Howard ◽  
Timothy R. Fennell ◽  
Rodney W. Snyder ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Receptor Antagonists ◽  
Kappa Opioid ◽  
Duration Of Action ◽  
Opioid Receptor Antagonists ◽  
Plasma Pharmacokinetics ◽  
Pharmacokinetics In Rats

scholarly journals Behavioral Pharmacology of Novel Kappa Opioid Receptor Antagonists in Rats

2019 ◽  
Author(s):  
Sarah Page ◽  
Maria M Mavrikaki ◽  
Tania Lintz ◽  
Daniel Puttick ◽  
Edward Roberts ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Time Course ◽  
Kappa Opioid Receptor ◽  
Tail Flick ◽  
Receptor Antagonists ◽  
Kappa Opioid ◽  
Duration Of Action ◽  
Opioid Receptor Antagonists ◽  
Opioid Receptor Agonists ◽  
Self Stimulation

Abstract Background New treatments for stress-related disorders including depression, anxiety, and substance use disorder are greatly needed. Kappa opioid receptors are expressed in the central nervous system, including areas implicated in analgesia and affective state. Although kappa opioid receptor agonists share the antinociceptive effects of mu opioid receptor agonists, they also tend to produce negative affective states. In contrast, selective kappa opioid receptor antagonists have antidepressant- and anxiolytic-like effects, stimulating interest in their therapeutic potential. The prototypical kappa opioid receptor antagonists (e.g., norBNI, JDTic) have an exceptionally long duration of action that complicates their use in humans, particularly in tests to establish safety. This study was designed to test dose- and time-course effects of novel kappa opioid receptor antagonists with the goal of identifying short-acting lead compounds for future medication development. Methods We screened 2 novel, highly selective kappa opioid receptor antagonists (CYM-52220 and CYM-52288) with oral efficacy in the warm water tail flick assay in rats to determine initial dose and time course effects. For comparison, we tested existing kappa opioid receptor antagonists JDTic and LY-2456302 (also known as CERC-501 or JNJ-67953964). Results In the tail flick assay, the rank order of duration of action for the antagonists was LY-2456302 < CYM-52288 < CYM-52220 << JDTic. Furthermore, LY-2456302 blocked the depressive (anhedonia-producing) effects of the kappa opioid receptor agonist U50,488 in the intracranial self-stimulation paradigm, albeit at a higher dose than that needed for analgesic blockade in the tail flick assay. Conclusions These results suggest that structurally diverse kappa opioid receptor antagonists can have short-acting effects and that LY-2456302 reduces anhedonia as measured in the intracranial self-stimulation test.

scholarly journals Discovery ofN-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists

2013 ◽  
Vol 56 (11) ◽  
pp. 4551-4567 ◽  
Author(s):  
Chad M. Kormos ◽  
Chunyang Jin ◽  
Juan Pablo Cueva ◽  
Scott P. Runyon ◽  
James B. Thomas ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Receptor Antagonists ◽  
Kappa Opioid ◽  
Opioid Receptor Antagonists

Kappa opioid receptor antagonists

Peptides 1994 ◽  
1995 ◽  
pp. 607-608
Author(s):  
G. Orosz ◽  
A. Z. Rónai ◽  
E. Kátay ◽  
K. Medzihradszky
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Receptor Antagonists ◽  
Kappa Opioid ◽  
Opioid Receptor Antagonists
Sign in / Sign up

Export Citation Format

Share Document