scholarly journals Synthesis and evaluation of sigma receptor ligands

2010 ◽  
Author(s):  
◽  
Kuo-Hsien Fan
Keyword(s):  
Sigma Receptor ◽  
Imaging Agents ◽  
Receptor Ligands ◽  
Receptor Ligand ◽  
Sigma 1 Receptor ◽  
Lead Compounds ◽  
In Vivo Distribution ◽  
Sigma 1

Sigma receptors are unique binding sites located in the central nervous system (CNS) and peripheral organs. Two sigma receptor subtypes ([signma]1 and [sigma]2) have been described so far. It is known that the [sigma]1 receptor is involved in a number of CNS disorders and the [sigma]2 receptor is involved in tumor proliferation among others. Because of the important biological functions of the [sigma] receptor, development of structure activity relationships (SAR) can aid in the identification of potential medications and imaging agents. Three series of analogs based on three lead compounds have been synthesized and evaluated for their in vitro affinity and selectivity for the [sigma]1 and [sigma]2 subtypes. Lead I is a selective [sigma]1 receptor ligand with anti-cocaine activity, but its in vivo distribution is unknown. Our in vitro binding results showed that all the Lead I analogs are potent [sigma]1 receptor ligands. Furthermore, one of the Lead I analogs was radioiodinated and evaluated for its in vivo distribution. In vivo evaluation of the radioiodinated Lead I analog has shown high brain uptake and specific binding to [sigma]1 receptor of the radioligand. Lead II is also a selective [sigma]1 receptor ligand and radioiodinated Lead II has been shown to be a potential imaging agent for the [sigma]1 receptor. Two of the Lead II analogs were shown to be potent [sigma]1 receptor ligands. The radioiodinated Lead II analogs were demonstrated to be potential imaging agents for [sigma]1 receptor in vivo. Lead III is one of the most selective [sigma]2 receptor ligands known to date. Only one of the newly synthesized Lead III analogs was found to be a selective [sigma]2 receptor ligand. The SAR study of Lead III analogs successfully indentified the important structural features in Lead III for [sigma]2 receptor binding. To summarize, the SAR studies based on the lead compounds have generated useful information and three potential [sigma]1 imaging agents were prepared in the studies.

The activity of selective sigma-1 receptor ligands in seizure models in vivo

2017 ◽  
Vol 328 ◽  
pp. 13-18 ◽  
Author(s):  
Edijs Vavers ◽  
Baiba Svalbe ◽  
Lasma Lauberte ◽  
Ilmars Stonans ◽  
Ilga Misane ◽  
...  
Keyword(s):  
Receptor Ligands ◽  
Sigma 1 Receptor ◽  
Seizure Models ◽  
Sigma 1

[ 11 C]Raclopride binding was reduced in vivo by sigma 1 receptor ligand SA4503 in the mouse brain, while [ 11 C]SA4503 binding was not by raclopride

2001 ◽  
Vol 28 (7) ◽  
pp. 787-792 ◽  
Author(s):  
Kiichi Ishiwata ◽  
Tadayuki Kobayashi ◽  
Kazunori Kawamura ◽  
Kiyoshi Matsuno ◽  
Michio Senda
Keyword(s):  
Mouse Brain ◽  
Receptor Ligand ◽  
Sigma 1 Receptor ◽  
Sigma 1

scholarly journals N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jose A. Morales-Garcia ◽  
Javier Calleja-Conde ◽  
Jose A. Lopez-Moreno ◽  
Sandra Alonso-Gil ◽  
Marina Sanz-SanCristobal ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Spatial Learning And Memory ◽  
South American ◽  
New Production ◽  
Sigma 1 Receptor ◽  
Neurogenic Niche ◽  
Sigma 1 ◽  
Functional Relevance

Abstract N,N-dimethyltryptamine (DMT) is a component of the ayahuasca brew traditionally used for ritual and therapeutic purposes across several South American countries. Here, we have examined, in vitro and vivo, the potential neurogenic effect of DMT. Our results demonstrate that DMT administration activates the main adult neurogenic niche, the subgranular zone of the dentate gyrus of the hippocampus, promoting newly generated neurons in the granular zone. Moreover, these mice performed better, compared to control non-treated animals, in memory tests, which suggest a functional relevance for the DMT-induced new production of neurons in the hippocampus. Interestingly, the neurogenic effect of DMT appears to involve signaling via sigma-1 receptor (S1R) activation since S1R antagonist blocked the neurogenic effect. Taken together, our results demonstrate that DMT treatment activates the subgranular neurogenic niche regulating the proliferation of neural stem cells, the migration of neuroblasts, and promoting the generation of new neurons in the hippocampus, therefore enhancing adult neurogenesis and improving spatial learning and memory tasks.

scholarly journals SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo

2003 ◽  
Vol 88 (3) ◽  
pp. 438-446 ◽  
Author(s):  
Y Berthois ◽  
B Bourrié ◽  
S Galiègue ◽  
H Vidal ◽  
P Carayon ◽  
...  
Keyword(s):  
Sigma Receptor ◽  
Receptor Ligand

scholarly journals In vitro and in vivo sigma 1 receptor imaging studies in different disease states

2020 ◽  
Author(s):  
Hebaalla Agha ◽  
Christopher R. McCurdy
Keyword(s):  
Clinical Trials ◽  
Molecular Imaging ◽  
Receptor Imaging ◽  
Imaging Studies ◽  
Sigma 1 Receptor ◽  
The Road ◽  
Disease States ◽  
Sigma 1

Molecular imaging studies have paved the road for the development of successful σ1R ligands currently in clinical trials.

scholarly journals Highly Specific Sigma Receptor Ligands Exhibit Anti-viral Properties in SARS-CoV-2 Infected Cells

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1514
Author(s):  
David A. Ostrov ◽  
Andrew P. Bluhm ◽  
Danmeng Li ◽  
Juveriya Qamar Khan ◽  
Megha Rohamare ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Sigma Receptor ◽  
Sigma Receptors ◽  
Genome Replication ◽  
Receptor Ligands ◽  
Sigma 1 Receptor ◽  
Binding Characteristics ◽  
Sigma Receptor Ligands ◽  
Prevention And Treatment ◽  
Sigma 1

(1) Background: There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present in the replication complex. (2) Methods: In this work, highly specific sigma receptor ligands were investigated for their ability to inhibit both SARS-CoV-2 genome replication and virus induced cellular toxicity. This study found antiviral activity associated with agonism of the sigma-1 receptor (e.g., SA4503), ligation of the sigma-2 receptor (e.g., CM398), and a combination of the two pathways (e.g., AZ66). (3) Results: Intermolecular contacts between these ligands and sigma receptors were identified by structural modeling. (4) Conclusions: Sigma receptor ligands and drugs with off-target sigma receptor binding characteristics were effective at inhibiting SARS-CoV-2 infection in primate and human cells, representing a potential therapeutic avenue for COVID-19 prevention and treatment.

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