Department of Drug Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Medical University of Warsaw, 1, Banacha Street, 02-097 Warsaw, Poland.
Published: March 2019
AI Article Synopsis
Article Abstract
The study enabled obtaining a number of new derivatives of 4-aryl-pyrido[1,2-c]pyrimidine 9.1-9.27 having conformationally restricted tryptamine moiety. In vitro studies (RBA) have shown that derivatives 9.1, 9.2, 9.4, 9.7, 9.9, 9.14 and 9.27 exhibit high affinity to molecular targets 5-HT receptor and SERT protein. In general, compounds with an unsubstituted or a para-substituted benzene ring of the pyrido[1,2-c]pyrimidine residue in the terminal part were characterized by higher binding ability, which can be justified by the greater flexibility of the structure. For the selected compounds 9.1, 9.7, 9.9 and 9.27, further in vitro, in vivo and metabolic stability tests were performed. The in vitro studies in the extended receptor profile (D, 5-HT, 5-HT and 5-HT) indicated their selectivity toward the 5-HT receptor and SERT protein. The in vivo studies (8-OH-DPAT-induced hypothermia in mice, FST) revealed that the compound 9.1 has the properties of presynaptic agonist of the 5-HT receptor, and compound 9.7 demonstrated the properties of a presynaptic antagonist of the 5-HT receptor. Metabolic stability studies, in turn, showed that compounds 9.1, 9.7 and 9.9, having an unsubstituted indole residue, were more resistant to biotransformation reactions of the first pass phase than was compound 9.27 containing a 5-methoxy-substituted indole residue. The obtained results allowed further optimization of the structure.
Major depressive disorder (MDD) is one of the most common diseases affecting millions of people worldwide. The use of existing antidepressants in many cases does not allow achieving stable remission, probably due to insufficient understanding of pathological mechanisms. This indicates the need for the development of more effective drugs based on in-depth understanding of MDD's pathophysiology.
Ketamine displays efficacious rapid-acting antidepressant (RAAD) activity in the rat chronic mild stress (CMS) model. It rapidly reverses anhedonia (CMS-induced sucrose consumption deficit) and attenuates working memory deficit (novel object recognition: NOR) following both systemic (intraperitoneal, i.p.
Following a decades-long decline in psychedelic research resulting from social, political, and legislative factors, there has been greatly renewed interest in these compounds' ability to treat psychiatric disorders. Classic psychedelics, encompassing both natural and synthetic psychoactive compounds, are characterized by their action as agonists or partial agonists of serotonin 5-hydroxytryptamine 2A receptors. In this comprehensive review, we summarize the latest clinical trials of classic psychedelics on depression and anxiety, attending to the patient demographics and methodology of each study.
Background: Maintaining gut microbial homeostasis is crucial for human health, as imbalances in the gut microbiota (GM) can lead to various diseases, including metabolic syndrome (MS), exacerbated by the use of antipsychotic medications such as olanzapine (OLZ). Understanding the role of the GM in OLZ-induced MS could lead to new therapeutic strategies. This study used metagenomic analysis to explore the impact of OLZ on the GM composition and examined how probiotics can mitigate its adverse effects in a rat model.
Background: Although some studies suggest that sleep deprivation may affect ejaculation regulation, related research is limited, and the mechanisms remain unclear.
Aim: This study aimed to explore whether sleep deprivation influences ejaculation regulation through amyloid-beta and to investigate its potential mechanisms.
Materials And Methods: Normal ejaculating rats were randomly distributed into three separate groups for the study, and treated with sleep deprivation combined with saline gavage, sleep deprivation combined with sodium butyrate gavage, and control with saline gavage.
