Tert-butyl 4-((1-phenyl-1H-pyrazol-4-yl) methyl) piperazine-1-carboxylate (LQFM104)- New piperazine derivative with antianxiety and antidepressant-like effects: Putative role of serotonergic system.

Autor: da Silva DM; Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Sanz G; Chemistry Institute, Laboratory of Chromatography and Mass Spectrometry, Federal University of Goiás, Goiânia, GO, Brazil., Vaz BG; Chemistry Institute, Laboratory of Chromatography and Mass Spectrometry, Federal University of Goiás, Goiânia, GO, Brazil., de Carvalho FS; Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil., Lião LM; Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil., de Oliveira DR; Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Moreira LKDS; Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Cardoso CS; Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., de Brito AF; Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., da Silva DPB; Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., da Rocha FF; Department of Physiological Sciences, Institute of Biology, Federal Rural University of Rio de Janeiro, Seropédica, RJ, Brazil., Santana IGC; Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Galdino PM; Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Costa EA; Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil. Electronic address: xico@ufg.br., Menegatti R; Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goiás, Goiânia, GO, Brazil.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2018 Jul; Vol. 103, pp. 546-552. Date of Electronic Publication: 2018 Apr 24.
DOI: 10.1016/j.biopha.2018.04.077
Abstrakt: The piperazine derivatives correspond to an extensive chemical class of compounds with numerous neuropharmacological activities, including antidepressant (e.g., nefazodone, trazodone) and anxiolytic (e.g., buspirone) properties. Therefore, aiming to identify a new antidepressant and antianxiety lead-compound, our group designed, synthesized, and investigated the effects of a new piperazine compound, namely, LQFM104, on the behavior of mice. Male albino Swiss mice were treated with LQFM104 prior to predictive behavioral tests as open field (OFT), elevated plus maze (EPM), forced swimming (FST), and tail suspension tests (TST). The participation of the serotonergic system was evaluated by pretreatment with a 5-HT1A antagonist receptor (WAY100635) and serotonin (5-HT) synthesis inhibitor (p-chlorphenylalanine, pCPA) before oral administration of LQFM104 and behavioral tests. The treatment with LQFM104 did not interfere with locomotor activity but revealed suggestive data of anxiolytic-like effects by the increase in the time spent in the center of the OFT. This activity was confirmed by the results obtained in the EPM, and it was abolished after pretreatment with WAY100635 and pCPA. The immobility time decreased in both the FST and TST. The antidepressant-like activity was completely abolished after WAY100635 pretreatment. Altogether, these data revealed that LQFM104 possesses anxiolytic and antidepressant-like properties in behavioral tests on mice, and these activities are possibly mediated, directly and/or indirectly, by serotonergic pathways.
(Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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