nmda agonist

AIMS: The N-methyl-D-aspartate (NMDA) receptor (NMDAR) has been proven to be strongly correlated with rapid antidepressant effects. Here, GW043, as a new compound targeting NMDAR, we explored its antidepressant effects and its mechanism of action. METHODS: Our study utilized electrophysiological techniques to confirm the effect of GW043 on NMDAR currents. Additionally, we assessed the selectivity of GW043 through high-throughput receptor-ligand binding experiments...

Microdosing ketamine is a novel antidepressant for treatment-resistant depression. Traditional antidepressants, like selective serotonin reuptake inhibitors (SSRIs), inhibit serotonin reuptake, but it is not clear if ketamine shows a similar mechanism. Here, we tested the effects of feeding ketamine and SSRIs to Drosophila melanogaster larvae, which has a similar serotonin system to mammals and is a good model to track depressive behaviors, such as locomotion and feeding. Fast-scan cyclic voltammetry (FSCV) was used to measure optogenetically stimulated serotonin changes, and locomotion tracking software and blue dye feeding to monitor behavior...

INTRODUCTION: Precipitated opioid withdrawal syndrome (OWS) is a severe and intolerable situation that may occur by a pharmaceutical agent. Reactivation of inhibited N-methyl-d-aspartate (NMDA) receptor in person with prolonged opioid use can led to severe OWS. We conducted a double-blind, randomized clinical trial to assess the effect of magnesium sulfate (MGSO4 ) as an NMDA receptor antagonist on OWS. MATERIALS AND METHODS: The study randomly divided forty patients with precipitated OWS due to partial agonist (buprenorphine) use referred to the emergency unit of Toxicology Department of Mashhad University of Medical Sciences, Iran; into two groups...

Glutamatergic synapses encode information from extracellular inputs using dynamic protein interaction networks (PINs) that undergo widespread reorganization following synaptic activity, allowing cells to distinguish between signaling inputs and generate coordinated cellular responses. Here, we investigate how Fragile X Messenger Ribonucleoprotein (FMRP) deficiency disrupts signal transduction through a glutamatergic synapse PIN downstream of NMDA receptor or metabotropic glutamate receptor (mGluR) stimulation...

Serine proteases regulate cell functions through G protein-coupled protease-activated receptors (PARs). Cleavage of one peptide bond of the receptor amino terminus results in the formation of a new N-terminus ("tethered ligand") that can specifically interact with the second extracellular loop of the PAR receptor and activate it. Activation of PAR1 by thrombin (canonical agonist) and activated protein C (APC, noncanonical agonist) was described as a biased agonism. Here, we have supposed that synthetic peptide analogs to the PAR1 tethered ligand liberated by APC could have neuroprotective effects like APC...

Hydrogen sulfide (H2 S) and polysulfides (H2 Sn , n ≥ 2) produced by enzymes play a role as signalling molecules regulating neurotransmission, vascular tone, cytoprotection, inflammation, oxygen sensing, and energy formation. H2 Sn , which have additional sulfur atoms to H2 S, and other S-sulfurated molecules such as cysteine persulfide and S-sulfurated cysteine residues of proteins, are produced by enzymes including 3-mercaptopyruvate sulfurtransferase (3MST). H2 Sn are also generated by the chemical interaction of H2 S with NO, or to a lesser extent with H2 O2 ...

Cholinergic innervation of the hippocampus correlates with memory formation. In a well-established animal model of type 1 diabetes mellitus, obtained by injecting young adult rats with streptozotocin (STZ), reductions have been reported in the expression of acetylcholine receptors and choline acetyltransferase. In this study, we showed that long-term synaptic depression (LTD) induced by carbachol (CCh), a nonselective cholinergic receptor agonist, at Schaffer collateral-CA1 synapses in hippocampal slices was significantly weaker in streptozotocin-induced diabetic rats (STZ rats) than in age-matched control rats...

The given investigation examined the neuroprotection role of 5-HT1b/1d agonist in reserpine induced Parkinson's disease (PD) in male Wistar rats. PD was induced in rats by reserpine at 5 mg/kg ip for 3 days and thereafter the rats were provided with the following treatments for 4 days, zolmitriptan (ZLM) group (30 mg/kg ip); STD group (levodopa + carbidopa, 200 + 5 mg/kg ip); ZLM + GA group (zolmitriptan, 30 mg/kg ip and glutamic acid, 1...

N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation mediates glutamate (Glu) toxicity and involves bleomycin (BLM)-induced acute lung injury (ALI). We have reported that bone marrow-derived mesenchymal stem cells (BM-MSCs) are NMDAR-regulated target cells, and NMDAR activation inhibits the protective effect of BM-MSCs on BLM-induced pulmonary fibrosis, but its effect on ALI remains unknown. Here, we found that Glu release was significantly elevated in plasma of mice at d 7 after intratracheally injected with BLM...

Astrocytes are pivotal for synaptic transmission and may also play a role in the induction and expression of synaptic plasticity, including endocannabinoid-mediated long-term depression (eCB-LTD). In the dorsolateral striatum (DLS), eCB signaling plays a major role in balancing excitation and inhibition and promoting habitual learning. The aim of this study was to outline the role of astrocytes in regulating eCB signaling in the DLS. To this end, we employed electrophysiological slice recordings combined with metabolic, chemogenetic and pharmacological approaches in an attempt to selectively suppress astrocyte function...

In an effort to further understand the challenges facing in vivo imaging probe development for the N-methyl-D-aspartate (NMDA) receptor ion channel, we have evaluated the effect of glutamate on the Alzheimer's disease (AD) brain. Human post-mortem AD brain slices of the frontal cortex and anterior cingulate were incubated with [3 H]MK-801 and adjacent sections were tested for Aβ and Tau. The binding of [3 H]MK-801 was measured in the absence and presence of glutamate and glycine. Increased [3 H]MK-801 binding in AD brains was observed at baseline and in the presence of glutamate, indicating a significant increase (>100%) in glutamate-induced NMDA ion channel activity in AD brains compared to cognitively normal brains...

The partial N-methyl-D-aspartate receptor (NMDAR) agonist D-Cycloserine (DCS) has been evaluated for the treatment of a wide variety of psychiatric disorders, including dementia, schizophrenia, depression and for the augmentation of exposure-based psychotherapy. Most if not all of the potential psychiatric applications of DCS target an enhancement or restitution of cognitive functions, learning and memory. Their molecular correlate is long-term synaptic plasticity; and many forms of synaptic plasticity depend on the activation of NMDA receptors...

The normal function of the N-methyl D-aspartate receptors (NMDAR) in human lungs depends on precisely regulated synaptic glutamate levels. Pathophysiology of the lungs is brought on by the changes in homeostasis of glutamate in the synapsis that leads to abnormal NMDAR activity. Severe acute respiratory syndrome (SARS) primarily results in lung infections, particularly lung muscle stiffening, and NMDA receptor potentiation may increase calcium ion influx and support downstream signaling mechanisms. Hence, NMDAR modulators that depend on glutamate levels could be therapeutically useful medications with fewer unintended side effects...

BACKGROUND: N-methyl-D-aspartate receptor (NMDAR) are amino acid receptors that are well studied in brain physiology; however, their role in kidney is poorly understood. Nonetheless, NMDAR inhibitors can increase serum K+ and reduce GFR, which suggests they have an important physiological role in the kidney. We hypothesized that NMDARs in the distal nephron induce afferent-arteriole vasodilation through the vasodilator mechanism connecting-tubule-glomerular feedback (CNTGF) that involves ENaC activation...

The hormone leptin reduces food intake through actions in the peripheral and central nervous system, including in the hindbrain nucleus of the solitary tract (NTS). The NTS receives viscerosensory information via vagal afferents, including information from the gastrointestinal tract, which is then relayed to other CNS sites critical for control of food intake. Leptin receptors (lepRs) are expressed by a subpopulation of NTS neurons, and knockdown of these receptors increases both food intake and body weight...

Adenosine triphosphate (ATP) changes the efficacy of synaptic transmission. Despite recent progress in terms of the roles of purinergic receptors in cerebrocortical excitatory synaptic transmission, their contribution to inhibitory synaptic transmission is unknown. To elucidate the effects of α,β-methylene ATP (αβ-mATP), a selective agonist of P2X receptors (P2XRs), on inhibitory synaptic transmission in the insular cortex (IC), we performed whole-cell patch-clamp recording from IC pyramidal neurons (PNs) and fast-spiking neurons (FSNs) in either sex of VGAT-Venus transgenic rats...

Two cardinal elements in the complex and multifaceted pathophysiology of schizophrenia (SCZ) are neuroinflammation and dysregulation of glutamatergic neurotransmission, with the latter being especially involved in treatment-resistant schizophrenia (TRS). Interestingly, the Kynurenine (KYN) pathway (KP) is at the crossroad between them, constituting a potential causal link and a therapeutic target. Although there is preclinical and clinical evidence indicating a dysregulation of KP associated with the clinical phenotype of SCZ, clinical studies investigating the possible relationship between changes in biomarkers of the KP and response to pharmacotherapy are still limited...

The current study was designed to examine the role of glutamate NMDA receptors of the mediodorsal thalamus (MD) in scopolamine-induced memory impairment. Adult male rats were bilaterally cannulated into the MD. According to the results, intraperitoneal (i.p.) administration of scopolamine (1.5 mg/kg) immediately after the training phase (post-training) impaired memory consolidation. Bilateral microinjection of the glutamate NMDA receptors agonist, N-Methyl-D-aspartic acid (NMDA; 0.05 µg/rat), into the MD significantly improved scopolamine-induced memory consolidation impairment...

Background and Purpose P2X4 receptors (P2X4R) are ligand gated cation channels that are activated by extracellular adenosine 5'-triphosphate (ATP) released by neurons and glia. The receptors are widely expressed in the brain and have fractional calcium currents comparable to NMDA receptors. Although P2X4Rs were described to modulate synaptic transmission and plasticity, their involvement in shaping neuronal network activity remains to be elucidated. Exp. Approach We investigated the effects of P2X receptors on network and synaptic level using local field potential electrophysiology, whole cell patch clamp recordings and calcium imaging in fast spiking parvalbumin positive interneurons (PVINs) in rat and mice hippocampal slices...

In the last years, neuroprotective therapies have attracted the researcher interests as modern and challenging approach for the treatment of neurodegenerative diseases, aimed at protecting the nervous system from injuries. Glaucoma is a neurodegenerative disease characterized by progressive excavation of the optic nerve head, retinal axonal injury and corresponding vision loss that affects millions of people on a global scale. The molecular basis of the pathology is largely uncharacterized yet, and the therapeutic approaches available do not change the natural course of the disease...