Major Depressive Disorder and Kappa Opioid Receptor

Li, Wei; Huijiao, Sun; Hao, Chunyan; Yang, Xiao; Li, Xiao; Liu, Renyu; Shao, Liming; Zhuibai, Qiu

doi:10.31480/2330-4871/035

Cited by 4 publications

(2 citation statements)

References 54 publications

(65 reference statements)

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“…This dual action places buprenorphine in a unique position, not only addressing the core issue of opioid dependency but also potentially ameliorating accompanying mood disturbances, an aspect not typically addressed by traditional opioid agonists. κ-opioid receptor antagonists are also being explored for their potential in treatment of depressive disorders [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Buprenorphine in Depression: A Meta-Analysis of Current Evidence

Bhivandkar,

Sarfraz,

Jain

et al. 2024

J Clin Med Res

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Background Emerging research indicates buprenorphine, used in management of opioid use disorder, has attracted interest for its potential in treating a variety of psychiatric conditions. This meta-analysis aimed to determine the efficacy of buprenorphine in treating symptoms of depression. Methods Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a search was conducted of several databases until April 25, 2022, for English language articles related to buprenorphine and its use in treating various mental health conditions. Standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were reported for the Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS) scores. Statistical analyses were performed using Cochrane RevMan 5. Results Of the 1,347 identified studies, six clinical trials were included. MADRS-10 least square mean difference (LSMD) inter-group assessment favored buprenorphine over placebo, but it lacked statistical significance. Similarly, MADRS scores as well as HAM-D inter-group assessment were in favor of buprenorphine, however, were not statistically significant. These findings suggest a potential therapeutic role for buprenorphine in treating depression, albeit with caution due to the observed lack of statistical significance and the potential for confounding factors. Conclusions Preliminary evidence suggests potential efficacy of buprenorphine at lower doses in improving improving outcomes specifically related to depression. However, due to limitations in statistical significance and possible confounding factors, entail cautious interpretation. Further rigorous research is needed to investigate the long-term effects, optimal dosing, and determine the role of adjuvant drug therapy.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Buprenorphine in Depression: A Meta-Analysis of Current Evidence

Bhivandkar,

Sarfraz,

Jain

et al. 2024

J Clin Med Res

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“…The use of KOR agonists in animals and humans can produce anxiety and depression-like effects [ 90 ] whereas KOR antagonists demonstrate a reliable antidepressant effect in animal models [ 91 ]. Although no KOR antagonists are currently in clinical use, formulations such as buprenorphine, ALKS5461, and CERC-501 are in clinical trials and have good antidepressant effects [ 92 ]. It is believed that in the future, short-acting KOR antagonists may be developed to treat depression.…”

Section: Discussionmentioning

confidence: 99%

Potential biomarkers: differentially expressed proteins of the extrinsic coagulation pathway in plasma samples from patients with depression

Zhang

Shi

et al. 2021

Bioengineered

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Depression is a severe disabling psychiatric illness and the pathophysiological mechanisms remain unknown. In previous work, we found the changes in extrinsic coagulation (EC) pathway proteins in depressed patients compared with healthy subjects were significant. In this study, we screened differentially expressed proteins (DEPs) in the EC pathway, and explored the molecular mechanism by constructing a protein-protein interaction (PPI) network. The DEPs of the EC pathwaywere initially screened by isobaric tags for relative and absolute quantification (iTRAQ) in plasma samples obtained from 20 depression patients and 20 healthy controls, and were then identified by Enzyme-linked immunosorbent assays (ELISAs). Ingenuity Pathway Analysis (IPA) software was used to analyse pathway. The differentially expressed genes (DEGs) were identified by analyzing the GSE98793 microarray data from the Gene Expression Omnibus database using the Significance Analysis for Microarrays (SAM, version 4.1) statistical method. Cytoscape version 3.4.0 software was used to construct and visualize PPI networks. The results show that Fibrinogen alpha chain (FGA), Fibrinogen beta chain (FGB), Fibrinogen gamma chain (FGG) and Coagulation factor VII (FVII) were screened in the EC pathway from depression patient samples. FGA, FGB, and FGG were significantly up-regulated, and FVII was down-regulated. Thirteen DEGs related to depression and EC pathways were identified from the microarray database. Among them NF-κB Inhibitor Beta (NFKBIB) and Heat shock protein family B (small) member 1 (HSPB1) were highly correlated with EC pathway. We conclude that EC pathway is associated with depression, which provided clues for the biomarker development and the pathogenesis of depression.

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Development of Novel Quinoxaline-Based κ-Opioid Receptor Agonists for the Treatment of Neuroinflammation

et al. 2018

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Neuroinflammatory disorders, such as multiple sclerosis or experimental autoimmune encephalomyelitis (EAE), an established mouse model mimicking part of the human pathology, are characterized by inflammatory infiltrates containing T helper 1 (TH1) and TH17 cells, which cause demyelination and neurodegeneration. Disease onset and perpetuation are mediated by peripherally generated autoreactive T cells infiltrating into the central nervous system, where they are restimulated by antigen-presenting cells. Here, we show that newly designed peripherally active, potent, and selective κ-opioid receptor (KOR) agonists comprising the ethylenediamine KOR pharmacophore in a perhydroquinoxaline scaffold exhibit potent anti-inflammatory capacities in primary antigen presenting cells as well as T cells. In the EAE model, the secondary amine 12 and the triazole 14 were able to ameliorate disease severity and to delay disease onset by blocking effector T cell activation. Importantly, the beneficial effects were mediated via signaling through KOR because off-target effects were excluded by using KOR-deficient mouse mutants.

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Major Depressive Disorder and Kappa Opioid Receptor

Cited by 4 publications

References 54 publications

Therapeutic Potential of Buprenorphine in Depression: A Meta-Analysis of Current Evidence

Therapeutic Potential of Buprenorphine in Depression: A Meta-Analysis of Current Evidence

Potential biomarkers: differentially expressed proteins of the extrinsic coagulation pathway in plasma samples from patients with depression

Development of Novel Quinoxaline-Based κ-Opioid Receptor Agonists for the Treatment of Neuroinflammation

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