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Antidepressant-like effects of BU10119, a novel buprenorphine analogue with mixed ?/? receptor antagonist properties, in mice.
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ABSTRACT: Background and purpose
The ? receptor antagonists have potential for treating neuropsychiatric disorders. We have investigated the in vivo pharmacology of a novel buprenorphine analogue, BU10119, for the first time.Experimental approach
To determine the opioid pharmacology of BU10119 (0.3-3 mg·kg-1 , i.p.) in vivo, the warm-water tail-withdrawal assay was applied in adult male CD1 mice. A range of behavioural paradigms was used to investigate the locomotor effects, rewarding properties and antidepressant or anxiolytic potential of BU10119. Additional groups of mice were exposed to a single (1 × 2 h) or repeated restraint stress (3× daily 2 h) to determine the ability of BU10119 to block stress-induced analgesia.Key results
BU10119 alone was without any antinociceptive activity. BU10119 (1 mg·kg-1 ) was able to block U50,488, buprenorphine and morphine-induced antinociception. The ? antagonist effects of BU10119 in the tail-withdrawal assay reversed between 24 and 48 h. BU10119 was without significant locomotor or rewarding effects. BU10119 (1 mg·kg-1 ) significantly reduced the latency to feed in the novelty-induced hypophagia task and reduced immobility time in the forced swim test, compared to saline-treated animals. There were no significant effects of BU10119 in either the elevated plus maze or the light-dark box. Both acute and repeated restraint stress-induced analgesia were blocked by pretreatment with BU10119 (1 mg·kg-1 ). Parallel stress-induced increases in plasma corticosterone were not affected.Conclusions and implications
BU10119 is a mixed ?/? receptor antagonist with relatively short-duration ? antagonist activity. Based on these preclinical data, BU10119 has therapeutic potential for the treatment of depression and other stress-induced conditions.Linked articles
This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.
SUBMITTER: Almatroudi A
PROVIDER: S-EPMC6016679 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
Publications
Antidepressant-like effects of BU10119, a novel buprenorphine analogue with mixed κ/μ receptor antagonist properties, in mice.
British journal of pharmacology 20171106 14
<h4>Background and purpose</h4>The κ receptor antagonists have potential for treating neuropsychiatric disorders. We have investigated the in vivo pharmacology of a novel buprenorphine analogue, BU10119, for the first time.<h4>Experimental approach</h4>To determine the opioid pharmacology of BU10119 (0.3-3 mg·kg<sup>-1</sup> , i.p.) in vivo, the warm-water tail-withdrawal assay was applied in adult male CD1 mice. A range of behavioural paradigms was used to investigate the locomotor effects, rew ...[more]