MF-8, a novel promising arylpiperazine-hydantoin based 5-HT7 receptor antagonist: In vitro drug-likeness studies and in vivo pharmacological evaluation

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.

Keywords: 5-HT7 receptor antagonist; Antidepressant-like activity; Anxiolytic-like activity; Arylpiperazines; Drug-like properties.