Antidepressant-like effects of BU10119, a novel buprenorphine analogue with mixed κ/μ receptor antagonist properties, in mice

Abdulrahman Mohammed I Almatroudi, Mehrnoosh Ostovar, Christopher Bailey, Stephen Husbands, Sarah Bailey

Research output: Contribution to journalArticle

13 Citations (Scopus)
55 Downloads (Pure)

Abstract

Background and Purpose: 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. 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 κ 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 κ/μ receptor antagonist with relatively short-duration κ 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.

Original languageEnglish
Pages (from-to)2869-2880
Number of pages12
JournalBritish Journal of Pharmacology
Volume175
Issue number14
Early online date1 Oct 2017
DOIs
Publication statusPublished - 1 Jul 2018

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Antidepressant-like effects of BU10119, a novel buprenorphine analogue with mixed κ/μ receptor antagonist properties, in mice'. Together they form a unique fingerprint.

Cite this