Sigma and Mental Disorders

Published research to date related to Sigma proteins and Mental Disorders has been conducted with compounds not developed by Advantx Pharmaceuticals Inc. Our therapeutic candidate ADV127 is the first truly selective, pharmaceutical-grade compound in development targeting the Sigma-1 receptor with a clean molecule and unambiguous agonist activity, far superior in potency, selectivity, safety, and efficacy to all others tested to date.


Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus

By Peng Ren, Jing-Ya Wang, Hong-Lei Chen, Yue Wang, Lin-Yu Cui, Jing-Yao Duan, Wen-Zhi Guo, Yong-Qi Zhao, and Yun-Feng Li Excerpt from the article published in Journal of Pharmacological Sciences, Volume 154, Issue 4, April 2024, Pages 236-245, ISSN 1347-8613, DOI: Abstract Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. […]

Sigma-1 receptor activation mediates the sustained antidepressant effect of ketamine in mice via increasing BDNF levels

By Hui Ma, Jin-feng Li, Xin Qiao, Yue Zhang, Xiao-juan Hou, Hai-xia Chang, Hong-lei Chen, Yong Zhang, and Yun-feng Li Excerpt from the article published in Acta Pharmacologica Sinica 45, 704–713 (2024). DOI: Abstract Sigma-1 receptor (S1R) is a unique multi-tasking chaperone protein in the endoplasmic reticulum. Since S1R agonists exhibit potent antidepressant-like activity, […]

Sigma receptor ligands are potent anti-prion compounds that act independently of sigma receptor binding

By Robert C. C. Mercer, Nhat T. T. Le, Mei C. Q. Houser, Aaron B. Beeler, and David A. Harris Excerpt from the article published in bioRxiv 2023.11.28.569035; November 29, 2023. DOI: Editor’s Highlights Abstract Prion diseases are invariably fatal neurodegenerative diseases of humans and other animals for which there are no treatment options. Previous work from […]

Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment

By Giuseppe De Simone, Benedetta Mazza, Licia Vellucci, Annarita Barone, Mariateresa Ciccarelli, and Andrea de Bartolomeis Excerpt from the article published in Antioxidants 12, 21 April 2023, no. 4: 975. DOI: Editor’s Highlights Abstract Schizophrenia is a worldwide mental illness characterized by alterations at dopaminergic and glutamatergic synapses resulting in global dysconnectivity within and between […]

Gut microbiota from sigma-1 receptor knockout mice induces depression-like behaviors and modulates the cAMP/CREB/BDNF signaling pathway

By Jia-Hao Li, Jia-Li Liu, Xiu-Wen Li, Yi Liu, Jian-Zheng Yang, Li-Jian Chen, Kai-Kai Zhang, Xiao-Li Xie, and Qi Wang Excerpt from the article published in Frontiers in Microbiology, 06 April 2023, Sec. Evolutionary and Genomic Microbiology, Volume 14 – 2023, DOI: Editor’s Highlights Abstract Introduction: Depression is a common mental disorder that affects approximately 350 […]

Gender and Neurosteroids: Implications for Brain Function, Neuroplasticity, and Rehabilitation

By Loredana Raciti, Caterina Formica, Gianfranco Raciti, Angelo Quartarone, and Rocco Salvatore Calabrò Excerpt from the article published in the International Journal of Molecular Sciences. 2023; 24(5):4758. 1 March 2023. DOI: Editor’s Highlights Abstract Neurosteroids are synthesized de novo in the nervous system; they mainly moderate neuronal excitability, and reach target cells via the […]

SSRIs differentially modulate the effects of pro-inflammatory stimulation on hippocampal plasticity and memory via sigma 1 receptors and neurosteroids

By Yukitoshi Izumi, Angela M. Reiersen, Eric J. Lenze, Steven J. Mennerick, and Charles F. Zorumski Excerpt from the article published in Translational Psychiatry 13, 39, 03 February 2023, DOI: Editor’s Highlights Abstract Certain selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory effects in preclinical models, and recent clinical studies suggest that fluvoxamine can prevent deterioration […]

Sigma-1 Receptor as a Protective Factor for Diabetes-Associated Cognitive Dysfunction via Regulating Astrocytic Endoplasmic Reticulum-Mitochondrion Contact and Endoplasmic Reticulum Stress

By Mengyu Du, Tao Jiang, Shuxuan He Bo Cheng, Xin Zhang, Liya Li, Lan Yang, Wei Gao, Yansong Li, and Qiang Wang Excerpt from the article published in Cells 2023, 12(1), 197; 3 January 2023, DOI: Editor’s Highlights Abstract The prevalence of diabetes-associated cognitive dysfunction (DACD) has increased to 13.5%. Dementia, as the most severe DACD, […]

Protein Misfolding and Aggregation in the Brain: Common Pathogenetic Pathways in Neurodegenerative and Mental Disorders

By Aleksandra Ochneva, Yana Zorkina, Olga Abramova, Olga Pavlova, Valeriya Ushakova, Anna Morozova, Eugene Zubkov, Konstantin Pavlov, Olga Gurina, and Vladimir Chekhonin Excerpt from the article published in International Journal of Molecular Sciences 23, no. 22: 14498.  21 November 2022, DOI: Editor’s Highlights Abstract Mental disorders represent common brain diseases characterized by substantial impairments of […]

Neurexin1α knockout rats display oscillatory abnormalities and sensory processing deficits back-translating key endophenotypes of psychiatric disorders

By Philipp Janz, Marie Bainier, Samuel Marashli, Philipp Schoenenberger, Miguel Valencia, and Roger L. Redondo Excerpt from the article published in Translational Psychiatry volume 12, Article number: 455, 28 October 2022, DOI: Editor’s Highlights Neurexins (NRXNs) are a large family of cell adhesion proteins that play a central role in synapse maturation and organization […]

Repeated inhibition of sigma-1 receptor suppresses GABAA receptor expression and long-term depression in the nucleus accumbens leading to depressive-like behaviors

By Yaoyao Qin, Weixing Xu, Kunpeng Li, Qi Luo, Xi Chen, Yue Wang, Lei Chen, and Sha Sha Excerpt from the article published in Frontiers in Molecular Neuroscience, 30 September 2022Sec. Brain Disease Mechanisms, DOI: Editor’s Highlights Abstract Sigma-1 receptor (σ1R) downregulation in male mice is known to cause a depressive-like phenotype. The nucleus […]

Sigma-1 receptor: A potential target for the development of antidepressants

By Yu-Ming Wang, Cong-Yuan Xi, Hong-Mei Jia, Jun He, Wen-Wen Lian, Yu Yan, Wen-Ping Wang, Wei-Ku Zhang, and Jie-Kun Xua Introduction to the article in Neurochemistry International, 8 July 2022, 105390, DOI: Autor’s Highlights The expression of Sigma-1 receptor is changed in animal models of depression and patients with depression. Activation of Sigma-1 receptor […]

The Link Between Energy-Related Sensations and Metabolism: Implications for Treating Fatigue

By Marco Filippi, Rainer Krähenmann, and Patrick Fissler Excerpt from the article published in Frontiers in Psychology, volume 13, 21 June 2022, DOI: Editor’s Highlights Physical exercise has been shown to improve energy-related sensations such as energetic arousal, calmness, burnout, emotional exhaustion, fatigue, and vigor. Evidence reveals a robust link between fatigue and different components […]

Sigma-1 Receptors in Depression: Mechanism and Therapeutic Development

By Peng Ren, Jingya Wang, Nanxi Li, Guangxiang Li, Hui Ma, Yongqi Zhao, and Yunfeng Li Excerpt from the article published in Frontiers on Pharmacology, 16 June 2022, Sec.Neuropharmacology, DOI: Editor’s Highlights Depression is a mainly persistent mood disorder that negatively impacts the social, vocational and educational aspects of people’s life. Sigma-1 receptors are […]

Inflammatory signaling mechanisms in bipolar disorder

By Gregory H. Jones, Courtney M. Vecera, Omar F. Pinjari, and Rodrigo Machado-Vieira Excerpt from the article published in Journal of Biomedical Science 28, 45, 11 June 2021, DOI: Editor’s Highlights Bipolar disorder (BD) is a highly complex, multifactorial disease with significant clinical heterogeneity, pleiotropy, and pathophysiological basis. Current first-line treatments, while helpful for […]

Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders

by Kinga Sałaciak, Karolina Pytka Excerpt from the article published in Neuroscience & Biobehavioral Reviews Volume 132, January 2022, ISSN 0149-7634, Editor’s Highlights Sigma-1 receptors are unique therapeutic targets modulating the activity of various proteins and systems in the organism. Preclinical studies reported that sigma-1 receptor expression correlates with the clinical manifestation of disease. […]

Involvement of Chaperone Sigma1R in the Anxiolytic Effect of Fabomotizole

By Mikhail V. Voronin, Yulia V. Vakhitova, Inna P. Tsypysheva, Dmitry O. Tsypyshev, Inna V. Rybina, Rustam D. Kurbanov, Elena V. Abramova, and Sergei B. Seredenin Excerpt from the article published in International Journal of Molecular Sciences 22, no. 11: 5455. Editor’s Highlights Epidemiological data indicate that the global prevalence of anxiety disorders reaches 7.3%. […]

Chaperone Sigma1R and Antidepressant Effect

By Mikhail V. Voronin, Yulia V. Vakhitova, and Sergei B. Seredenin Excerpt from the article published in International Journal of Molecular Sciences 2020 Oct; 21(19): 7088. Published 2020 Sep 25. DOI: 10.3390/ijms21197088 Editor’s Highlights Antidepressant use is accompanied by various side effects, and about one-third of patients do not achieve remission. Sigma-1 receptor (Sigma1R) acts as a chaperone to stabilize […]