Publications by authors named "Mikhail Y Dron"
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 PDFThe pharmacology of acid-sensitive ion channels (ASICs) is diverse, but potent and selective modulators, for instance for ASIC2a, are still lacking. In the present work we studied the effect of five 2-aminobenzimidazole derivatives on native ASICs in rat brain neurons and recombinant receptors expressed in CHO cells using the whole-cell patch clamp method. 2-aminobenzimidazole selectively potentiated ASIC3.
View Article and Find Full Text PDFArticle 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.
Article 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.