Beyond traditional therapies : Functionally selective compounds for fast antidepressant-like and procognitive effects

Description

Abstract Functional selectivity, a phenomenon where a ligand favors activation of specific signaling pathways over others, emerges as an innovative approach to neuropsychiatric challenges, especially depression and related cognitive impairments. This seminar will illuminate the complex interplay of the serotonin 5-HT1A receptor with multiple signaling pathways, resulting in diverse behavioral impacts. A detailed exploration of the cellular profiles of biased 5-HT1A receptor agonists such as NLX-101, NLX-204, and F13714 will be undertaken, along with a discussion on their pharmacological effects observed in rodents. Additionally, the seminar will delve into the unique pharmacological properties of HBK-15, a multimodal compound, which exhibits both rapid antidepressant-like and procognitive benefits in rodents.

Sałaciak, K. & Pytka, K. Biased agonism in drug discovery: Is there a future for biased 5-HT1A receptor agonists in the treatment of neuropsychiatric diseases? Pharmacol Therapeut 227:107872 (2021)

Sniecikowska, J. et al. Discovery of Novel pERK1/2- or β Arrestin-Preferring 5 HT1A Receptor-Biased Agonists: Diversified Therapeutic-like versus Side Effect Profile. J Med Chem 63, 10946–10971 (2020).

Pytka, K. et al. HBK-15, a multimodal compound, induces procognitive effects through modulating hippocampal LTP and enhancing theta-gamma coupling in mice. (2023) doi:10.21203/rs.3.rs-3126208/v1.