Molecules, Vol. 23, Pages 2926: Investigation of New Orexin 2 Receptor Modulators Using In Silico and In Vitro Methods

Molecules, Vol. 23, Pages 2926: Investigation of New Orexin 2 Receptor Modulators Using In Silico and In Vitro Methods Molecules doi: 10.3390/molecules23112926 Authors: Jana Janockova Rafael Dolezal Eugenie Nepovimova Tereza Kobrlova Marketa Benkova Kamil Kuca Jan Konecny Eva Mezeiova Michaela Melikova Vendula Hepnarova Avi Ring Ondrej Soukup Jan Korabecny The neuropeptides, orexin A and orexin B (also known as hypocretins), are produced in hypothalamic neurons and belong to ligands for orphan G protein-coupled receptors. Generally, the primary role of orexins is to act as excitatory neurotransmitters and regulate the sleep process. Lack of orexins may lead to sleep disorder narcolepsy in mice, dogs, and humans. Narcolepsy is a neurological disorder of alertness characterized by a decrease of ability to manage sleep-wake cycles, excessive daytime sleepiness, and other symptoms, such as cataplexy, vivid hallucinations, and paralysis. Thus, the discovery of orexin receptors, modulators, and their causal implication in narcolepsy is the most important advance in sleep-research. The presented work is focused on the evaluation of compounds L1–L11 selected by structure-based virtual screening for their ability to modulate orexin receptor type 2 (OX2R) in comparison with standard agonist orexin-A together with their blood-brain barrier permeability and cytotoxicity. We can conclude that the studied compounds possess an affinity towards t...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research