Central pharmacological activity of a new piperazine derivative: 4-(1-Phenyl-1h-pyrazol-4-ylmethyl)-piperazine-1-carboxylic acid ethyl ester

Brito, Adriane Ferreira de; Martins, José Luís Rodrigues; Fajemiroye, James Oluwagbamigbe; Galdino, Pablinny Moreira; Lima, Thereza Christina Monteiro de; Menegatti, Ricardo; Costa, Élson Alves

doi:10.1016/j.lfs.2012.04.037

Cited by 18 publications

(8 citation statements)

References 36 publications

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“…Hence, these results suggest that the anxiolytic‐like activity of LQFM032 is benzodiazepine site dependent. These results are different from the previous data which implicated 5‐HT 1A receptor in the anxiolytic‐like activity of LQFM008 (analog of LQFM032) …”

Section: Discussioncontrasting

confidence: 99%

“…In the present study, the treatment with LQFM032 decreased sleep latency and increase sleep time, thereby suggesting CNS depressant effect. This result is consistent with the previous data on LQFM008 which also demonstrated CNS depressant activity …”

Section: Discussionsupporting

confidence: 94%

“…This result is consistent with the previous data on LQFM008 which also demonstrated CNS depressant activity. [11] Compounds with central depressant activity may compromise exploratory activity, which could compromise the results in specific behavioral tests. Hence, open-field test was conducted to observe various behavioral parameters, such as rearings and numbers of crossings that indicate exploration activity, grooming number indicating stereotyped activity, among other behaviors including that may suggest an anxiolytic-like activity, which are number of crossings and time spent in the center of the open field.…”

Section: Discussionmentioning

confidence: 99%

“…These results are different from the previous data which implicated 5-HT 1A receptor in the anxiolytic-like activity of LQFM008 (analog of LQFM032). [11] Because the anxiolytic effects of classical agonists of benzodiazepines site are associated with undesirable anterograde amnesia, [35] it becomes necessary to evaluate the effect of LFQM032 on the performance of experimental animal's memory. In avoidance memory in step-down test, the treatment with LQFM032 increased the latency to stepdown compared with test session; however, the control group showed the same effect.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we describe the biological evaluation of a new heterocyclic piperazine derivative, LQFM 032 ( 4 ), which was designed from hybridization molecular strategy from LQFM008 ( 2 ) and JWB‐1‐84‐1 ( 3 )—lead compounds. LQFM 008 ( 2 ) is an anxiolytic and antidepressive‐like compound that was synthesized through molecular simplification of clozapine ( 1 ), while JWB‐1‐84‐1 ( 3 ) is an analog of acetylcholine with neuroprotective properties . As illustrated in Figure a, we changed ethyl 1‐piperazinacarboxylate C by 1‐(2‐hydroxyethyl)piperazine C.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2017

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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.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

et al. 2017

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A new piperazine derivative: 1-(4-(3,5-di-tert-butyl-4-hydroxybenzyl) piperazin-1-yl)-2-methoxyethan-1-one with antioxidant and central activity

Brito

Braga

Moreira

et al. 2017

Naunyn-Schmiedeberg's Arch Pharmacol

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In the scope of a research program aimed at developing new drugs for the treatment of central nervous system diseases, we describe herein the synthesis and pharmacological evaluation of 1-(4-(3,5-di-tert-butyl-4-hydroxybenzyl) piperazin-1-yl)-2-methoxyethan-1-one (LQFM180). This compound showed antioxidant activity in two models, electroanalytical assays, and DPPH activity. Moreover, in behavioral tests as the open field test LQFM180 (9.4, 18.8, and 37.6 mg/kg, per oral (p.o.)), we detected anxiolytic-like activity. In the sodium pentobarbital-induced sleep test, LQFM180, in all doses, decreased the latency to sleep and increased sleep duration, indicating central depressant activity; moreover, in the chimney test, LQFM180 did not alter motor activity. LQFM180 (18.8 mg/kg, p.o.) increased the time and number of entries on open arms in the elevated plus maze test, suggesting anxiolytic-like activity, which was reversed by NAN-190 and p-chlorophenylalanine, indicating a role of the serotonergic pathway on this effect. In the forced swimming test, LFQM180 (18.8 mg/kg, p.o.) decreased immobility time, suggesting antidepressant-like activity, which was reversed by monoaminergic antagonists, indicating a role for the serotonergic, noradrenergic, and dopaminergic pathways. Competition binding assays showed that LQFM180 was able to bind to the α, 5-HT, and D receptors, however, within the low micromolar range. We conclude that LQFM180 should be considered as a scaffold for drug candidate development.

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Preclinical data on morpholine (3,5-di-tertbutyl-4-hydroxyphenyl) methanone induced anxiolysis

Cabral

Moreira

Rodrigues

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Central pharmacological activity of a new piperazine derivative: 4-(1-Phenyl-1h-pyrazol-4-ylmethyl)-piperazine-1-carboxylic acid ethyl ester

Abstract: The compound LQFM008 showed anxiolytic-like activity which may involve serotonergic pathway.

Cited by 18 publications

References 36 publications

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

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

A new piperazine derivative: 1-(4-(3,5-di-tert-butyl-4-hydroxybenzyl) piperazin-1-yl)-2-methoxyethan-1-one with antioxidant and central activity

Preclinical data on morpholine (3,5-di-tertbutyl-4-hydroxyphenyl) methanone induced anxiolysis

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