Publications by authors named "Arseniy S Zhigulin"
Amidine-containing compounds are primarily known as antiprotozoal agents (pentamidine, diminazene, furamidine) or as serine protease inhibitors (nafamostat, sepimostat, camostat, gabexate). DAPI is widely recognized as a fluorescent DNA stain. Recently, it has been shown that these compounds also act as NMDA receptor inhibitors.
View Article and Find Full Text PDFMechanisms of NMDA Receptor Inhibition by Biguanide Compounds.
Pharmaceuticals (Basel)
September 2024
Article Synopsis
- - Recent research highlights the repurposing of NMDA receptor antagonists like ketamine for treating major depressive disorder, sparking renewed interest in studying NMDA receptors.
- - A study used whole-cell patch-clamp methods to evaluate the effects of biguanide compounds on NMDA receptors in rat hippocampal neurons, finding that certain compounds like cycloguanil, proguanil, and phenformin effectively inhibited these receptors.
- - The compounds were found to act as non-competitive inhibitors, with distinct mechanisms, suggesting their potential for treating neurodegenerative disorders linked to glutamatergic excitotoxicity and providing insights into NMDA receptor structure.
N-methyl-D-aspartate (NMDA) receptors are inhibited by many amidine and guanidine compounds. In this work, we studied the mechanisms of their inhibition by sepimostat-an amidine-containing serine protease inhibitor with neuroprotective properties. Sepimostat inhibited native NMDA receptors in rat hippocampal CA1 pyramidal neurons with IC of 3.
View Article and Find Full Text PDFArticle Synopsis
- Proton-gated ASIC channels are found in central neurons and are thought to be important for neurophysiological functions, though their exact roles are not fully understood.
- Acidification in the synaptic cleft affects glutamate receptors and ASICs differently, suggesting that ASICs might help balance post-synaptic responses during significant acidity levels.
- Research involving rat brain neurons indicates variability in ASIC and glutamate receptor responses, highlighting the influence of pH, magnesium, and membrane voltage on synaptic transmission and plasticity.
Febrile seizures (FSs) are a relatively common early-life condition that can cause CNS developmental disorders, but the specific mechanisms of action of FS are poorly understood. In this work, we used hyperthermia-induced FS in 10-day-old rats. We demonstrated that the efficiency of glutamatergic synaptic transmission decreased rapidly after FS by recording local field potentials.
View Article and Find Full Text PDFArticle Synopsis
- Acid-sensing ion channels (ASICs) are inhibited by various cationic compounds, and understanding how these compounds work can help in designing new drugs.
- In a study on serine protease inhibitors like nafamostat, sepimostat, and diminazene, it was found that they effectively blocked ASICs in rat brain cells, whereas camostat and gabexate showed little to no effect.
- Nafamostat, sepimostat, and diminazene demonstrated a voltage-dependent inhibition mechanism, suggesting potential for therapeutic use in conditions related to ASIC dysfunction, such as inflammatory pain and ischemic stroke.
Article Synopsis
- - NMDA receptor antagonists show potential in treating various central nervous system disorders, including major depressive disorder, and this study focuses on optimizing a specific biphenyl-based NMDA negative allosteric modulator (NAM).
- - The optimization process, guided by free energy calculations, resulted in a significant increase in activity, improving the compound's effectiveness by 100 times (IC = 50 nM) compared to an initial hit found through virtual screening.
- - Preliminary results indicate this optimized NAM has low affinity for the hERG ion channel, an earlier hurdle for similar compounds, and it exhibits a unique binding mode that differs from another related NMDA NAM called EVT-101.
Mechanisms of NMDA receptor inhibition by nafamostat, gabexate and furamidine.
Eur J Pharmacol
March 2022
N-methyl-D-aspartate (NMDA) receptors are affected by many pharmaceuticals. In this work, we studied the action of the serine protease inhibitors nafamostat, gabexate and camostat, and an antiprotozoal compound, furamidine, on native NMDA receptors in rat hippocampal pyramidal neurons. Nafamostat, furamidine and gabexate inhibited these receptors with IC values of 0.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates the effects of three antiprotozoal compounds (pentamidine, diminazene, and DAPI) on NMDA receptors in rat brain cells.
- All three compounds were found to inhibit NMDA receptor activity at specific concentrations, with distinct voltage dependencies in their actions.
- The differences in how these compounds interact with the NMDA receptors are attributed to their unique 3D structures, affecting their ability to be trapped in the receptor channels.