Prelegent: prof. Karol Bruzik (Department of Pharmaceutical Sciences, University of Illinois at Chicago)
Temat: GABA-A RECEPTOR AS A TARGET OF CNS DRUGS
Sterszczenie: The ligand-gated ion-channel, human brain GABAA receptor, is a complex collection of 19 molecular species comprising hetero-pentamers of several a, b, g, d and other protein subunits. GABAA receptor is a macromolecular target of a large variety of popular CNS drugs that include general anesthetics, anxiolytics, antidepressants and sedatives. Many of these drugs bind inside the specific interfaces that separate the various subunits, and most are positive allosteric modulators of GABA agonist action that affects ion-channel function of the receptor. Up until very recently, the paucity of structural data on the native brain receptor necessitated the use of photolabeling techniques combined with homology models based on simpler orthologs to determine the location and the makeup of the binding sites. In this series of four lectures, I will provide a chemist’s perspective on the inhibitory role of GABAA receptor in brain neural networks and its modulation by the allosteric ligands, as well as the current state-of-art in determining the location of binding sites of GABAA receptor ligands. I will discuss binding sites and pharmacology of the most popular drugs and their analogs such as propofol (Lecture 1), benzodiazepines (Lecture 2), etomidate and barbiturates (Lecture 3) and neurosteroids (Lecture 4). In Lecture 4, I will also provide an overview of the most recent advances in the structure-based design of new GABAAR ligands with positive allosteric modulatory properties (PAMs), and null allosteric ligands (NALs).
Data i godzina: 16 czerwca 2021 o godzinie 13.00
Miejsce: spotkanie online
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