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17 November 2022 - The 5-HT1A biased agonist, NLX-204, has rapid-acting antidepressant activity in mice

New data, just published in Behavioral Brain Research, shows robust activity of the Neurolixis drug development candidate, NLX-204, in two mouse models of depression. The peer-reviewed study, carried out in collaboration with the team of Dr. Karolina Pytka, at Jagiellonian University (Krakow, Poland) found that a single administration of NLX-204 was sufficient to completely abolish depression-like behaviors of mice subjected to chronic mild stress or to repeated administration of corticosterone, a pro-depressive substance. NLX-204 has previously been shown to posses strong antidepressant-like activity in naïve rats and 'biased agonist' activity at serotonin 5-HT1A receptors. The present study shows that its antidepressant properties are likely mediated by activation of specific cellular signaling mechanisms including phosphorylation of extracellular regulated kinase (ERK) and of cAMP response element-binding protein (CREB).

Depression is a major healthcare challenge affecting approximately 280 million people worldwide. Two-thirds of patients do not respond satisfactorily to current antidepressants, which require several weeks of administration before therapeutic onset, thus causing additional suffering for patients and their careers. Moreover, the COVID crisis has increased the incidence of depression and other affective disorders by nearly 30%.

Adrian Newman-Tancredi, CEO of Neurolixis, commented: “There is a large unmet medical need and market opportunity for an efficacious, rapid-acting and safe antidepressant to alleviate the suffering of millions of depressed patients. The promising results on NLX-204 suggest that it could constitute an innovative candidate for this indication and expand the Neurolixis 5-HT1A receptor 'biased agonist' development pipeline. ”

 The 5-HT1A receptor biased agonist, NLX-204, shows rapid-acting antidepressant-like properties and neurochemical changes in two mouse models of depression.

Głuch-Lutwin M, Sałaciak K, Pytka K, Gawalska A, Jamrozik M, Śniecikowska J, Kołaczkowski M, Depoortère RY, Newman-Tancredi A. 
Behav Brain Res. 2022 Nov 8:114207. (online ahead of print) doi: 10.1016/j.bbr.2022.114207. PMID: 36368443
 
The full publication is available with free access until 5th January 2023 on this link: https://authors.elsevier.com/a/1g5jgbrwfF0mS
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