Anxiolytic- and antidepressant-like effects of new phenylpiperazine derivative LQFM005 and its hydroxylated metabolite in mice

Moreira, Lorrane Kelle da Silva; Silva, Rafaela Ribeiro; Silva, Dayane Moreira da; Mendes, Mirella Andrade Silva; Brito, Adriane Ferreira de; Carvalho, Flávio Silva de; Sanz, Germán; Rodrigues, Marcella Ferreira; Silva, Artur Christian Garcia da; Thomaz, Douglas Vieira; Oliveira, Valéria de; Vaz, Boniek Gontijo; Lião, Luciano Morais; Valadares, Marize Campos; Gil, Eric de Souza; Costa, Élson Alves; Noël, François; Menegatti, Ricardo

doi:10.1016/j.bbr.2021.113582

Cited by 7 publications

(10 citation statements)

References 32 publications

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“…As a metabolite, it is assumed to be a less hydrophobic compound than LQFM05 and more easily eliminated from the body. Although the metabolite quantification was not the main purpose of the present study, the LQFM235 concentration was tentatively estimated in all tissues from in vivo rat samples ( Figure 6 ) as it also showed anxiolytic-like properties, as previously demonstrated [ 4 ]. Both LC-MS drug analyses were run under the same experimental conditions, meaning that the same sample preparation and instrumental conditions were used ( Section 3.4.2 ), except for the MRM transition ions of LQFM235 ( Figure 6 ).…”

Section: Resultsmentioning

confidence: 69%

“…In this sense, supplementary LC analysis of rat tissue samples also detected the 4-(4-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)−1H-pyrazol-1-yl)phenol (LQFM235) [ 4 ], a bioactive metabolite of the LQFM05 at 3.3 min ( Figure 6 ).…”

Section: Resultsmentioning

confidence: 99%

“…LQFM05 was synthesized at Laboratório de Química Farmacêutica Medicinal (LQFM, Universidade Federal de Goiás, Goiânia, Brazil). Purity (>98% ± 0.95 w / w ; n = 2) was determined by 1 H spectra, as described elsewhere [ 4 ].…”

Section: Methodsmentioning

confidence: 99%

“…Clozapine is the most used drug for schizophrenia disorder control, and is therefore constantly related to hematological and metabolic disorders as a side effect for some clinical patients [ 3 ], limiting its prescription and use. To fill this gap, 1-(4-methoxyphenyl)−4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazine (LQFM05) was investigated as a promising prototype antipsychotic N -phenylpiperazine drug, showing anxiolytic- and antidepressant-like effects in classical behavioral tests (12 or 24 µmol/kg LQFM005), putatively through activation of 5-HT1A receptors [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Bioanalytical LC-QTOF/MS Method for a N-phenylpiperazine Derivate (LQFM05): An Anxiolytic- and Antidepressant-like Prototype Drug Applied to Pharmacokinetic and Biodistribution Studies

et al. 2023

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The LQFM05 is a prototype drug designed for treatment of psychiatric disorders, such as schizophrenia, exhibiting anxiolytic- and antidepressant-like (12 or 24 µmol/kg) effects in classical behavioral tests. In order to evaluate its pharmacokinetic properties, a liquid chromatography method coupled to a quadrupole time of flight mass spectrometry system (LC-QTOF/MS) was developed and fully validated for LQFM05 analysis in rat plasma and tissue samples (brain, heart, liver, and kidneys). Liquid–liquid extraction, solid phase extraction and protein precipitation were assessed as clean-up procedures for biological samples and analyte enrichment. Plasma and tissue samples underwent protein precipitation as a preliminary step, using acetonitrile. Linearity was fully demonstrated for the dynamic range (10.0 to 900.0 ng/mL), with r2 values higher than 0.99 (RSDslope ≤ 2%, Fcal < Ftab, Ccal < Ctab). Biodistribution studies in rats revealed high brain tissue concentrations (12.4 µg/g), suggesting elevated drug affinity to the main therapeutic target tissue, showing a blood partition coefficient of 1.9. Kidneys also showed great exposure and tissue affinity, suggesting a potential extrahepatic clearance. Likewise, all examined tissues exhibited satisfactory LQFMF05 distribution. The mass fragmentation spectrum indicated the presence of its main metabolite, LQFM235, yielded by high hepatic hydroxylation route, an equally bioactive derivative. Lastly, the developed LC-QTOF/MS method was shown to be sensitive (LOQ = 10 ng/mL), precise and accurate for LQFM05 determination in tissue homogenates and plasma samples.

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Section: Resultsmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bioanalytical LC-QTOF/MS Method for a N-phenylpiperazine Derivate (LQFM05): An Anxiolytic- and Antidepressant-like Prototype Drug Applied to Pharmacokinetic and Biodistribution Studies

et al. 2023

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“…Nonetheless, the intrinsic physicochemical nature of the soil and the characteristics of the regional climate are known to play major roles in the organoleptic profile of wine grapes, as well as in the composition of their secondary metabolites [1]. In fact, several authors detailed the effects of soil organomineral content, acidity and alkalinity, moisture, temperature, as well as other factors in the stimulation of the phenylpropanoid metabolic pathway in grapes and other plants [2], thereby shedding light on the environmental influences on the aroma and mouthfeel of wines, as well as contributing to their chemical profiling according to geographic origin.…”

Section: Introductionmentioning

confidence: 99%

Redox Profiling of Selected Apulian Red Wines in a Single Minute

et al. 2022

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Wine is a complex bioproduct whose chemical composition is highly variable across production regions. In order to shed light on affordable ways to promote the characterization of wines and explore the physicochemical basis of their antioxidant capacity, this work reported on the quick and easy redox profiling of selected red wines from Apulia, Italy. Therefore, an affordable and quickly performed semiempirical quantum chemistry approach, i.e., the extended Hückel method, was used to compute the bandgaps of the main phytochemical markers attributed to red wines. The findings of these calculations were then compared to an electroanalytical investigation in the form of cyclic and square-wave voltammetry, and the electric current of the redox profiles was used as the input dataset for principal component analysis. Results showcased that the semiempirical quantum chemistry calculations allowed the correlation of the bandgaps to the observed faradaic signals upon voltammetry; thereby, also providing insights on their antioxidant appeal by highlighting the feasibility of charge-transfer processes at low electric potentials. Furthermore, the principal component analysis showed that the electric current dataset gathered in a time span of 55 s allowed the appropriate separation of the samples, which hints at the possible use of quick voltammetric assays as fingerprinting tools.

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Synthesis, characterization and antioxidative capacity of nickel(II) and zinc(II) complexes with 4-methylpyrazole

Kočović,

Holló,

Borišev

et al. 2025

Inorganica Chimica Acta

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Anxiolytic- and antidepressant-like effects of new phenylpiperazine derivative LQFM005 and its hydroxylated metabolite in mice

Cited by 7 publications

References 32 publications

Bioanalytical LC-QTOF/MS Method for a N-phenylpiperazine Derivate (LQFM05): An Anxiolytic- and Antidepressant-like Prototype Drug Applied to Pharmacokinetic and Biodistribution Studies

Bioanalytical LC-QTOF/MS Method for a N-phenylpiperazine Derivate (LQFM05): An Anxiolytic- and Antidepressant-like Prototype Drug Applied to Pharmacokinetic and Biodistribution Studies

Redox Profiling of Selected Apulian Red Wines in a Single Minute

Synthesis, characterization and antioxidative capacity of nickel(II) and zinc(II) complexes with 4-methylpyrazole

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