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

Abdulrahman Almatroudi, Mehrnoosh Ostovar, Christopher P Bailey, Stephen M Husbands, Sarah J Bailey

Research output: Contribution to journalArticlepeer-review


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

Original languageEnglish
Pages (from-to)2869-2880
Number of pages12
JournalBritish Journal of Pharmacology
Issue number14
Publication statusPublished - Jul 2018


  • Animals
  • Antidepressive Agents/therapeutic use
  • Anxiety/drug therapy
  • Behavior, Animal/drug effects
  • Buprenorphine/analogs & derivatives
  • Depression/drug therapy
  • Exploratory Behavior/drug effects
  • Locomotion/drug effects
  • Male
  • Mice
  • Pain/drug therapy
  • Receptors, Opioid, kappa/antagonists & inhibitors
  • Receptors, Opioid, mu/antagonists & inhibitors


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