AI Article Synopsis
- - NMDA receptors are crucial for many functions in the central nervous system (CNS), which has led to the need for specialized compounds that can modulate their activity.
- - Researchers discovered light-sensitive compounds derived from DENAQ that inhibit NMDA receptor activity, with structural variations significantly affecting their effectiveness and light sensitivity.
- - Among these compounds, PyrAQ showed the strongest effects, allowing for rapid and reversible NMDA receptor inhibition, making it a valuable tool for studying receptor function through light-based methods.
Article Abstract
NMDA receptors play critical roles in numerous physiological and pathological processes in CNS that requires development of modulating ligands. In particular, photoswitchable compounds that selectively target NMDA receptors would be particularly useful for analysis of receptor contributions to various processes. Recently, we identified a light-dependent anti-NMDA activity of the azobenzene-containing quaternary ammonium compounds DENAQ (diethylamine-azobenzene-quaternary ammonium) and DMNAQ (dimethylamine-azobenzene-quaternary ammonium). Here, we developed a series of light-sensitive compounds based on the DENAQ structure, and studied their action on glutamate receptors in rat brain neurons using patch-clamp method. We found that the activities of the compounds and the influence of illumination strongly depended on the structural details, as even minor structural modifications greatly altered the activity and sensitivity to illumination. The compound PyrAQ (pyrrolidine-azobenzene-quaternary ammonium) was the most active and produced fast and fully reversible inhibition of NMDA receptors. The IC values under ambient and monochromic light conditions were 2 and 14 μM, respectively. The anti-AMPA activity was much weaker. The action of PyrAQ did not depend on NMDA receptor activity, agonist concentration, or membrane voltage, making it a useful tool for photopharmacological studies.
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| http://dx.doi.org/10.1016/j.ejphar.2022.175448 | DOI Listing |
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