Molecular Insight into the Interaction between Different Classes of Psychoplastogens and Serotonin 5-HT2A Receptor

Medical treatment for behavioral disorders such as anxiety, depression, and post-traumatic stress disorder (PTSD) represent emerging challenges in the field and have been a subject of studies for a long time. Available therapeutics include selective serotonin reuptake inhibitors (SSRIs), Monoamine oxidase inhibitors (MAOIs), tricyclics, etc. Nevertheless, recent studies have identified a revolutionary new class of fast-acting antidepressants called psychoplastogens, which, unlike other conventional antidepressants, promote significant and long-lasting changes in neural plasticity during a single administration. In this study, we developed a novel classification of psychoplastogens based on their structural models. Moreover, we performed docking experiments to determine the binding energy of various classes of psychoplastogens to the serotonin 5-HT2A receptor. As a result, we identified a correlation between the hallucinogenic effect of some psychoplastogens we used in our docking study and their affinity to the 5-HT2A receptor. We then attempted to predict the patterns of binding affinities of newly generated psychoplastogens, which were validated using our methodology. It is expected that this study will provide insight into the future of in vitro research as well as potential clinical studies regarding psychoplastogens and provide a firm basis for the binding patterns related to these drugs in the human brain.