Anxiolytic-like effect of 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol is mediated through the benzodiazepine and nicotinic pathways

Brito, Adriane Ferreira de; Fajemiroye, James Oluwagbamigbe; Neri, Hiasmin Franciely da Silva; Silva, Dayane Moreira da; Silva, Daiany Priscilla Bueno da; Sanz Lobón, Germán; Vaz, Boniek Gontijo; Carvalho, Flávio Silva de; Ghedini, Paulo César; Liao, Luciano Morais; Menegatti, Ricardo; Costa, Elson Alves

Anxiolytic-like effect of 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol is mediated through the benzodiazepine and nicotinic pathways

Data

2017

Autores

Brito, Adriane Ferreira de

Fajemiroye, James Oluwagbamigbe

Neri, Hiasmin Franciely da Silva

Silva, Dayane Moreira da

Silva, Daiany Priscilla Bueno da

Sanz Lobón, Germán

Vaz, Boniek Gontijo

Carvalho, Flávio Silva de

Ghedini, Paulo César

Liao, Luciano Morais

Resumo

In this study, we proposed the design, synthesis of a new compound 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol (LQFM032), and pharmacological evaluation of its anxiolytic-like effect. This new compound was subjected to pharmacological screening referred to as Irwin test, prior to sodium pentobarbital-induced sleep, open-field and wire tests. The anxiolytic-like effect of this compound was evaluated using elevated plus maze and light–dark box tests. In addition, the mnemonic activity was evaluated through step-down test. In sodium pentobarbital-induced sleep test, LQFM032 decreased latency and increased duration of sleep. In the open-field test, LQFM032 altered behavioral parameter, that suggested anxiolytic-like activity, as increased in crossings and time spent at the center of open field. In the plus maze test and light–dark box test, the LQFM032 showed anxiolytic-like activity, increased entries and time spent on open arms, and increased in number of transitions and time spent on light area, respectively. Those effects was antagonized by flumazenil but not with 1-(2-Methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN-190). The LQFM032 did not alter mnemonic activity. Moreover, the anxiolytic-like activity of LQFM032 was antagonized by mecamylamine. In summary, LQFM032 showed benzodiazepine and nicotinic pathways mediated anxiolytic-like activity without altering the mnemonic activity.

Palavras-chave

benzodiazepine site, LQFM032, Nicotinic activity, Piperazine derivative

Citação

BRITO, Adriane F. et al. Anxiolytic-like effect of 2-(4-((1-Phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol is mediated through the benzodiazepine and nicotinic pathways. Chemical Biology & Drug Design, [s. l.], v. 90, n. 3, p. 432-442, 2017. DOI: 10.1111/cbdd.12961. Disponível em: https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.12961. Acesso em: 28 jun. 2023.