Biased 5-HT2A receptor agonists as potential therapeutic drugs for treatment-resistant neuropsychiatric disorders

The PhD project of Laura D’Andrea focused on designing and synthesizing 5-HT2A receptor agonists that might retain the introspective effects of psychedelics, while silencing hallucinations. The synthesized scaffolds were tested in vitro to verify their ability to bind the receptor, while displaying functional selectivity towards the recruitment of specific effector proteins, considered to be responsible for either the beneficial or undesired effects. Finally, a few of the synthesized compounds were proved to be the first β-arrestin-biased 5-HT2A receptor agonists reported to date, with the unique ability of selectively activating β-arrestin over Gαq, the latter being considered the main responsible for the sensorial distortion of perceived reality. The presentation will start with a brief introduction regarding the receptor, the outcomes of previous studies, and the final goal of her project, to then focus on the chemical synthesis of the prepared agonists.

The PhD study was completed at Department of Chemistry and Bioscience, Faculty of Engineering, Aalborg University.

This summary was prepared by the PhD student.