| Literature DB >> 29439902 |
Gniewomir Latacz1, Annamaria Lubelska2, Magdalena Jastrzębska-Więsek3, Anna Partyka3, Katarzyna Kucwaj-Brysz2, Anna Wesołowska3, Katarzyna Kieć-Kononowicz2, Jadwiga Handzlik4.
Abstract
We report the in vitro drug-likeness studies and in vivo pharmacological evaluation for a new potent 5-HT7 receptor antagonist MF-8 (5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5-methylhydantoin). The in vitro tests showed good permeability, very good metabolic stability, low risk of drug-drug interactions and satisfying safety profile. Moreover, MF-8 showed excellent antidepressant-like activity in the forced swim test in rodents and promising anxiolytic-like activity in the four-plate test in mice. Regarding the potent affinity, high selectivity and antagonistic activity of MF-8 for the 5-HT7 receptor as well as excellent drug - like properties in vitro and confirmed in vivo pharmacological activity, MF-8 should be considered as a very significant molecule in the search for a new class of anti-depressant drugs.Entities:
Keywords: 5-HT7 receptor antagonist; Antidepressant-like activity; Anxiolytic-like activity; Arylpiperazines; Drug-like properties
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Year: 2018 PMID: 29439902 DOI: 10.1016/j.bmcl.2018.02.003
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN: 0960-894X Impact factor: 2.823