Antidepressant-like effects of BU10119, a novel buprenorphine analogue with mixed κ/μ receptor antagonist properties, in mice
| Autor: | Sarah J. Bailey, Abdulrahman Mohammed I Almatroudi, Christopher P Bailey, Mehrnoosh Ostovar, Stephen M. Husbands |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Elevated plus maze medicine.drug_class Receptors Opioid mu Pain Anxiety Pharmacology Anxiolytic Mice 03 medical and health sciences 0302 clinical medicine In vivo Internal medicine medicine Animals Behavior Animal Depression business.industry Receptors Opioid kappa Antagonist Antidepressive Agents Buprenorphine 030104 developmental biology Endocrinology Opioid Exploratory Behavior Antidepressant Themed Section: Research Papers business Locomotion 030217 neurology & neurosurgery medicine.drug Behavioural despair test |
| Zdroj: | Almatroudi, A M I, Ostovar, M, Bailey, C, Husbands, S & Bailey, S 2018, ' Antidepressant-like effects of BU10119, a novel buprenorphine analogue with mixed κ/μ receptor antagonist properties, in mice ', British Journal of Pharmacology, vol. 175, no. 14, pp. 2869-2880 . https://doi.org/10.1111/bph.14060 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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