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Kobayashi, Tetsuya; Matsuno, Kiyoshi; Murai, Masaaki; Mita, Shiro

doi:10.1023/a:1027361101419

Cited by 44 publications

(11 citation statements)

References 26 publications

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“…or s.c. of (+)-pentazocine [ 93 , 94 ], which are much higher than used in the present study’s Sigma1R agonists. In addition, the acute administration of Sigma1R selective agonist SA4503 does not affect dopamine content in the rat striatum [ 96 ], which is consistent with that of the sham-operated animals in our study. Taken together with data obtained in a rotarod test, an increase in intrastriatal DA content is compatible with the neurorestorative effect.…”

Section: Discussionsupporting

confidence: 89%

Deferred Administration of Afobazole Induces Sigma1R-Dependent Restoration of Striatal Dopamine Content in a Mouse Model of Parkinson’s Disease

Kadnikov

Verbovaya

Воронков

et al. 2020

IJMS

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Previously, we demonstrated that the immediate administration of multitarget anxiolytic afobazole slows down the progression of neuronal damage in a 6-hydroxidodamine (6-OHDA) model of Parkinson’s disease due to the activation of chaperone Sigma1R. The aim of the present study is to evaluate the therapeutic potential of deferred afobazole administration in this model. Male ICR mice received a unilateral 6-OHDA lesion of the striatum. Fourteen days after the surgery, mice were treated with afobazole, selective Sigma1R agonist PRE-084, selective Sigma1R antagonist BD-1047, and a combination of BD-1047 with afobazole or PRE-084 for another 14 days. The deferred administration of afobazole restored the intrastriatal dopamine content in the 6-OHDA-lesioned striatum and facilitated motor behavior in rotarod tests. The action of afobazole accorded with the effect of Sigma1R selective agonist PRE-084 and was blocked by Sigma1R selective antagonist BD-1047. The present study illustrates the Sigma1R-dependent effects of afobazole in a 6-OHDA model of Parkinson’s disease and reveals the therapeutic potential of Sigma1R agonists in treatment of the condition.

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Section: Discussionsupporting

confidence: 89%

Deferred Administration of Afobazole Induces Sigma1R-Dependent Restoration of Striatal Dopamine Content in a Mouse Model of Parkinson’s Disease

Kadnikov

Verbovaya

Воронков

et al. 2020

IJMS

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“…Those results provided a possible protective mechanism of DM (antagonist of NMDA receptor may promote or allow dendritic spine maintenance) in our MDMA-induced monkey model. Also, DM has been reported to increase serotonin levels54, through activation of sigma-1 receptors, which has been shown to modulate monoamine neurotransmitter levels555657. This data suggested block of MDMA in DA and SERT will be compensated possibly by DM triggered release.…”

Section: Discussionmentioning

confidence: 90%

Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

Hsing

Liu

Weng

et al. 2016

Sci Rep

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3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate.

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“…The σ 1 R subtype is involved in the facilitation of cortical Dopamine [DA] transmission in the rat brain ( 342 ). σ 1 Rs are located in limbic areas, including nucleus accumbens [NAC] ( 343 ) and PFC, both of which are thought to be involved in schizophrenia ( 344 ).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Sigma receptors [σRs]: biology in normal and diseased states

Rousseaux

Greene

2015

Journal of Receptors and Signal Transduction

124

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This review compares the biological and physiological function of Sigma receptors [σRs] and their potential therapeutic roles. Sigma receptors are widespread in the central nervous system and across multiple peripheral tissues. σRs consist of sigma receptor one (σ1R) and sigma receptor two (σ2R) and are expressed in numerous regions of the brain. The sigma receptor was originally proposed as a subtype of opioid receptors and was suggested to contribute to the delusions and psychoses induced by benzomorphans such as SKF-10047 and pentazocine. Later studies confirmed that σRs are non-opioid receptors (not an µ opioid receptor) and play a more diverse role in intracellular signaling, apoptosis and metabolic regulation. σ1Rs are intracellular receptors acting as chaperone proteins that modulate Ca2+ signaling through the IP3 receptor. They dynamically translocate inside cells, hence are transmembrane proteins. The σ1R receptor, at the mitochondrial-associated endoplasmic reticulum membrane, is responsible for mitochondrial metabolic regulation and promotes mitochondrial energy depletion and apoptosis. Studies have demonstrated that they play a role as a modulator of ion channels (K+ channels; N-methyl-d-aspartate receptors [NMDAR]; inositol 1,3,5 triphosphate receptors) and regulate lipid transport and metabolism, neuritogenesis, cellular differentiation and myelination in the brain. σ1R modulation of Ca2+ release, modulation of cardiac myocyte contractility and may have links to G-proteins. It has been proposed that σ1Rs are intracellular signal transduction amplifiers. This review of the literature examines the mechanism of action of the σRs, their interaction with neurotransmitters, pharmacology, location and adverse effects mediated through them.

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Untitled

Cited by 44 publications

References 26 publications

Deferred Administration of Afobazole Induces Sigma1R-Dependent Restoration of Striatal Dopamine Content in a Mouse Model of Parkinson’s Disease

Deferred Administration of Afobazole Induces Sigma1R-Dependent Restoration of Striatal Dopamine Content in a Mouse Model of Parkinson’s Disease

Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

Sigma receptors [σRs]: biology in normal and diseased states

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