ArticleSchizophrenia bulletin2022
Allosteric Modulation of the Sigma-1 Receptor Elicits Antipsychotic-like Effects.
Article in Schizophrenia bulletin, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Review
- Neuromodulatory roles of the sigma-1 receptor in behavior and drug sensitization during development.Acta pharmacologica Sinica · 2026Article
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- Sigma receptor ligands in selected affective disorders, psychoses, and addictions - a narrative review.Pharmacological reports : PR · 2026Review
- Sigma-1 receptor positive allosteric modulator promotes neuronal survival and improves cognitive deficits in AD mice via sigma-1 receptor/ERK pathway.Acta pharmacologica Sinica · 2026Article
- Selective recognition memory impairment in mitochondrial hydroxylase Clk1 mutant mice, rescued by antipsychotics.Acta pharmacologica Sinica · 2026Article
- Discovery and proof-of-concept study of a novel highly selective sigma-1 receptor agonist for antipsychotic drug development.Acta pharmaceutica Sinica. B · 2025Article
- Sigma-1 Receptor Activation by Fluvoxamine Ameliorates ER Stress, Synaptic Dysfunction and Behavioral Deficits in a Ketamine Model of Schizophrenia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Mechanism of Efferocytosis in Determining Ischaemic Stroke Resolution-Diving into Microglia/Macrophage Functions and Therapeutic Modality.Molecular neurobiology · 2024Review
- Exploring the Association between Schizophrenia and Cardiovascular Diseases: Insights into the Role of Sigma 1 Receptor.Physiological research · 2023Review
- Sigma-1 receptor and seizures.Pharmacological research · 2023Review
- The Missing Piece? A Case for Microglia's Prominent Role in the Therapeutic Action of Anesthetics, Ketamine, and Psychedelics.Neurochemical research · 2023Review
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allosteric modulation represents an important approach in drug discovery because of its advantages in safety and selectivity. SOMCL-668 is the first selective and potent sigma-1 receptor allosteric modulator, discovered in our laboratory. The present work investigates the potential therapeutic effects of SOMCL-668 on phencyclidine (PCP)-induced schizophrenia-related behavior in mice and further elucidates underlying mechanisms for its antipsychotic-like effects. SOMCL-668 not only attenuated acute PCP-induced hyperactivity and PPI disruption, but also ameliorated social deficits and cognitive impairment induced by chronic PCP treatment. Pretreatment with the selective sigma-1 receptor antagonist BD1047 blocked the effects of SOMCL-668, indicating sigma-1 receptor-mediated responses. This was confirmed using sigma-1 receptor knockout mice, in which SOMCL-668 failed to ameliorate PPI disruption and hyperactivity induced by acute PCP and social deficits and cognitive impairment induced by chronic PCP treatment. Additionally, in vitro SOMCL-668 exerted positive modulation of sigma-1 receptor agonist-induced intrinsic plasticity in brain slices recorded by patch-clamp. Furthermore, in vivo lower dose of SOMCL-668 exerted positive modulation of improvement in social deficits and cognitive impairment induced by the selective sigma-1 agonist PRE084. Also, SOMCL-668 reversed chronic PCP-induced down-regulation in expression of frontal cortical p-AKT/AKT, p-CREB/CREB and BDNF in wide-type but not sigma-1 knockout mice. Moreover, administration of the PI3K/AKT inhibitor LY294002 abolished amelioration by SOMCL-668 of chronic PCP-induced schizophrenia-related behaviors by inhibition of BDNF expression. The present data provide initial, proof-of-concept evidence that allosteric modulation of the sigma-1 receptor may be a novel approach for the treatment of psychotic illness.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.