GluN2 Subunit-Dependent Redox Modulation of NMDA Receptor Activation by Homocysteine

Homocysteine (HCY) molecule combines distinct pharmacological properties as an agonist of N-methyl-d-aspartate receptors (NMDARs) and a reducing agent. Whereas NMDAR activation by HCY was elucidated, whether the redox modulation contributes to its action is unclear. Here, using patch-clamp recording and imaging of intracellular Ca2+, we study dithiothreitol (DTT) effects on currents and Ca2+ responses activated by HCY through native NMDARs and recombinant diheteromeric GluN1/2A, GluN1/2B, and GluN1/2C receptors. Within a wide range (1–800 μM) of [HCY]s, the concentration–activation relationships for recombinant NMDARs revealed a biphasicness. The high-affinity component obtained between 1 and 100 µM [HCY]s corresponding to the NMDAR activation was not affected by 1 mM DTT. The low-affinity phase observed at [HCY]s above 200 μM probably originated from thiol-dependent redox modulation of NMDARs. The reduction of NMDAR disulfide bonds by either 1 mM DTT or 1 mM HCY decreased GluN1/2A currents activated by HCY. In contrast, HCY-elicited GluN1/2B currents were enhanced due to the remarkable weakening of GluN1/2B desensitization. In fact, cleaving NMDAR disulfide bonds in neurons reversed the HCY-induced Ca2+ accumulation, making it dependent on GluN2B- rather than GluN2A-containing NMDARs. Thus, estimated concentrations for the HCY redox effects exceed those in the plasma during intermediate hyperhomocysteinemia but may occur during severe hyperhomocysteinemia.

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Intrathecal Amitriptyline Acts as an N-Methyl-D-Aspartate Receptor Antagonist in the Presence of Inflammatory Hyperalgesia in Rats

Anesthesiology ◽

10.1097/00000542-199511000-00018 ◽

1995 ◽

Vol 83 (5) ◽

pp. 1046-1054 ◽

Cited By ~ 111

Author(s):

James C. Eisenach ◽

G. F. Gebhart

Keyword(s):

Nmda Receptor ◽

Tricyclic Antidepressants ◽

Hippocampal Slices ◽

Receptor Activation ◽

Affinity Binding ◽

Inflammatory Hyperalgesia ◽

High Affinity ◽

Aspartate Receptor ◽

Nmda Receptor Activation

Abstract Background Amitriptyline and other tricyclic antidepressants exhibit high affinity binding to N-methyl-D-aspartate (NMDA) receptors in vitro and inhibit NMDA receptor activation-induced neuroplasticity in hippocampal slices. Because spinal NMDA receptor activation is believed to be central to generation and maintenance of hyperalgesic pain, the purpose of this study was to test whether intrathecal amitriptyline reduced inflammation-induced hyperalgesia in the rat.

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Pharmacologically potentials of different substituted coumarin derivatives

10.31221/osf.io/w6hdg ◽

2019 ◽

Cited By ~ 1

Author(s):

Chem Int

Keyword(s):

Benzene Ring ◽

Bioactive Compounds ◽

Biological Activities ◽

Pharmacological Properties ◽

Coumarin Derivatives ◽

Wide Range ◽

Anti Oxidant ◽

Anti Inflammatory ◽

Coumarin Compounds

Coumarin and its derivatives are widely spread in nature. Coumarin goes to agroup as benzopyrones, which consists of a benzene ring connected to a pyronemoiety. Coumarins displayed a broad range of pharmacologically useful profile.Coumarins are considered as a promising group of bioactive compounds thatexhibited a wide range of biological activities like anti-microbial, anti-viral,antiparasitic, anti-helmintic, analgesic, anti-inflammatory, anti-diabetic, anticancer,anti-oxidant, anti-proliferative, anti-convulsant, and antihypertensiveactivities etc. The coumarin compounds have immense interest due to theirdiverse pharmacological properties. In particular, these biological activities makecoumarin compounds more attractive and testing as novel therapeuticcompounds.

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Faculty Opinions recommendation of Estradiol-induced enhancement of fear extinction in female rats: The role of NMDA receptor activation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733261946.793567213 ◽

2019 ◽

Author(s):

Amy Milton

Keyword(s):

Nmda Receptor ◽

Receptor Activation ◽

Fear Extinction ◽

Female Rats ◽

Nmda Receptor Activation

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A Brief Review on the Development of Novel Potentially Active Azetidin-2-ones Against Cancer

Current Organic Chemistry ◽

10.2174/1385272824666200303115444 ◽

2020 ◽

Vol 24 (5) ◽

pp. 473-486 ◽

Cited By ~ 1

Author(s):

Ligia S. da Silveira Pinto ◽

Thatyana R. Alves Vasconcelos ◽

Claudia Regina B. Gomes ◽

Marcus Vinícius N. de Souza

Keyword(s):

Side Effects ◽

Anticancer Agents ◽

Heterocyclic Compounds ◽

Biological Activities ◽

Present Review ◽

Pharmacological Properties ◽

Important Group ◽

Wide Range ◽

Anti Inflammatory

Azetidin-2-ones (β-lactams) and its derivatives are an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, anticancer, anti-diabetic, anti-inflammatory and anticonvulsant. Efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. The present review aimed to highlight some recent discoveries (2013-2019) on the development of novel azetidin-2-one-based compounds as potential anticancer agents.

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Tricyclic Pyrazole-Based Compounds as Useful Scaffolds for Cannabinoid CB1/CB2 Receptor Interaction

Molecules ◽

10.3390/molecules26082126 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2126

Author(s):

Battistina Asproni ◽

Gabriele Murineddu ◽

Paola Corona ◽

Gérard A. Pinna

Keyword(s):

Neuropathic Pain ◽

Cannabinoid Receptor ◽

Receptor Interaction ◽

Pharmacological Properties ◽

Cb2 Receptor ◽

Antiemetic Effect ◽

High Affinity ◽

Cb1 Antagonist ◽

Cb2 Receptors ◽

Sar Study

Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB1 and/or CB2 receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB1 antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB1 or CB2 receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.

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Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health

npj Schizophrenia ◽

10.1038/s41537-021-00151-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Nicolette Stogios ◽

Alexander Gdanski ◽

Philip Gerretsen ◽

Araba F. Chintoh ◽

Ariel Graff-Guerrero ◽

...

Keyword(s):

Metabolic Syndrome ◽

Autonomic Dysfunction ◽

Symptom Severity ◽

Sympathetic Activity ◽

Antipsychotic Treatment ◽

Autonomic Activity ◽

Autonomic Nervous System Dysfunction ◽

High Affinity ◽

Increased Risk ◽

Wide Range

AbstractSchizophrenia (SCZ) is a psychiatric disorder characterized by a wide range of positive, negative and cognitive symptoms, along with an increased risk of metabolic syndrome and cardiovascular disease that contribute to a 15–20-year reduced life expectancy. Autonomic dysfunction, in the form of increased sympathetic activity and decreased parasympathetic activity, is postulated to be implicated in SCZ and its treatment. The aim of this narrative review is to view SCZ through an autonomic lens and synthesize the evidence relating autonomic dysfunction to different domains of SCZ. Using various methods of assessing autonomic activity, autonomic dysfunction was found to be associated with multiple aspects of SCZ pathophysiology, including symptom severity, cognitive impairment, and the development of cardiometabolic comorbidities, such as metabolic syndrome and high BMI. The strongest association of low heart rate variability was noted among patients on antipsychotic treatment with high-affinity muscarinic antagonism (i.e., clozapine, olanzapine and quetiapine). The review will also suggest ways in which studying autonomic dysfunction can help reduce morbidity and mortality associated with SCZ and its treatment.

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