Potential antidepressant-like effect of piperazine derivative LQFM212 in mice: Role of monoaminergic pathway and brain-derived neurotrophic factor.

Autor: Moreira LKDS; Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil., de Brito AF; Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil., da Silva DM; Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil., Siqueira L; Laboratory of Medicinal Pharmaceutical Chemistry, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil., da Silva DPB; Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil., Cardoso CS; Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil., Florentino IF; Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil., de Carvalho PMG; Center for Biological and Health Sciences, Federal University of Western Bahia, Barreiras, BA, Brazil., Ghedini PC; Biochemical and Molecular Pharmacology Laboratory, Institute of Biological Sciences, Federal University of Goias, Campus Samambaia, Goiânia, GO, Brazil., Menegatti R; Laboratory of Medicinal Pharmaceutical Chemistry, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil., Costa EA; Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil. Electronic address: xico@ufg.br.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2021 Mar 05; Vol. 401, pp. 113066. Date of Electronic Publication: 2020 Dec 14.
DOI: 10.1016/j.bbr.2020.113066
Abstrakt: Major depression disorder (MDD) is one of the most widespread and debilitating psychiatric diseases and may be associated with other mental disorders such as anxiety. Despite advances in neurobiology studies, currently no established mechanism can explain all facets of MDD, and available drugs often show therapeutic delay for clinical effectiveness and response rates in patients are around 50 %. Previous activities of piperazine derivatives on CNS are indicators of its therapeutic potential for treating mental disorders. In this regard, we have previously shown that the piperazine derivative 2,6-di-tert-butyl-4-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)phenol (LQFM212) has anxiolytic-like activity which involves serotonergic pathway, nicotinic receptors and BZD-site of GABA A receptor, without cognitive impairments. Herein, was evaluated the potential antidepressant-like effect of LQFM212 on forced swimming test (FST) after a single dose of 54 μmol/kg and after repeated treatment for 15 days in mice. Pretreatment with WAY-100635, PCPA, prazosin, SCH-23390, sulpiride or AMPT reversed the antidepressant-like effect on FST, suggesting that monoaminergic pathway contributes for effects of LQFM212. Furthermore, repeated treatment with LQFM212 increased hippocampal BDNF levels dosed by ELISA kit. In assessment of possible adverse effects, repeated treatment with LQFM212 did not alter the body weight of the animals, glutathione levels in the liver, and serum levels of AST, ALT, urea, and creatinine. Taken together, the results showed that LQFM212 has an antidepressant-like effect that involves monoaminergic pathway and increased BDNF levels. This compound represents promising candidate for prototype of psychoactive drugs for treatment of anxiety and depression disorders since these pathological conditions may exist in comorbidities.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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