ИСТИНА

Ionotropic glutamate receptors play a primary role in excitatory neurotransmission. That implies the possibility to treat various neurological impairments via their inhibition. Perampanel is a first in class drug acting as AMPA type glutamate receptor antagonist for epilepsy treatment. It shows higher potency compared to its close structural analogs. Perampanel-like structures are also potential antagonists for NMDA type glutamate receptors where the subtype selectivity may be expected. Understanding the mechanisms underlying the biological action of perampanel-like structures is important for the design of new NMDA receptors antagonists. Since the available structural data is of low quality the accurate modeling of protein-ligand interactions requires the complex analysis to be performed. In current work we performed a conformational analysis of the set of perampanel-like structures at the DFT level. The docking study was carried out to reveal AMPA and NMDA receptors binding modes for perampanel and its analogs. Based on the results obtained the explanation of higher perampanel activity on AMPA receptors was proposed. The features of binding of perampanel-like molecules to AMPA and NMDA receptors were revealed.