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Elson Alves Costa - One of the best experts on this subject based on the ideXlab platform.

  • neuropharmacological assessment in mice and molecular docking of Piperazine Derivative lqfm212
    Behavioural Brain Research, 2020
    Co-Authors: Lorrane Kelle Da Silva Moreira, Adriane Ferreira De Brito, Crisciele Fontana, Flavio Souza De Carvalho, German Sanz, Luciano M Liao, Fabio Fagundes Da Rocha, Hugo Verli, Ricardo Menegatti, Elson Alves Costa
    Abstract:

    Abstract Piperazine Derivatives are an attractive class of chemical compounds for the treatment of various mental illness. Herein, we demonstrated the synthesis of LQFM212, a Piperazine Derivative, behavioral evaluation in mice and computational studies. In neuropharmacological assessment, LQFM212 treatment at doses of 18, 54 or 162 μmol/kg increased the sleep duration in sodium pentobarbital-induced sleep test. LQFM212 at dose of 162 μmol/kg increased climbing time in the chimney test and decreased the number of squares crossed in the open field test, suggesting that LQFM212 in high doses reduces spontaneous movement. However, LQFM212 treatment at the doses of 18 or 54 μmol/kg increased the preference for the center of field which could be indicative of anxiolytic-like effects. In elevated plus maze and light-dark box tests, LQFM212 treatment altered all parameters observed that demonstrate anxiolytic-like activity. These effects were reversed by flumazenil, mecamylamine, WAY-100635 and PCPA, but not with ketanserin, showing that anxiolytic-like activity involve benzodiazepine site of GABAA receptor, nicotinic and serotonergic pathways. Molecular docking of LQFM212 showed that the ligand has more interactions with GABAA receptor than with 5-HT1A receptor. Despite the involvement of benzodiazepine site on anxiolytic-like effect of LQFM212, treatment with this compound did not alter cognitive function in the step-down avoidance test. In this sense, this Piperazine Derivative is a good prototype for treating anxiety disorders with putative mechanism of action.

  • anti inflammatory effect of a new Piperazine Derivative 4 methylpiperazin 1 yl 1 phenyl 1h pyrazol 4 yl methanone
    Inflammopharmacology, 2018
    Co-Authors: Daniel Da Costa Batista, German Sanz, Luciano M Liao, Elson Alves Costa, Daiany P B Silva, Iziara F Florentino, Carina Sofia Cardoso, Merita P Goncalves, Marize Campos Valadares, Ricardo Menegatti
    Abstract:

    This study investigates the anti-nociceptive and anti-inflammatory effects of new Piperazine compound (LQFM182) as well as the toxicity acute in vitro. To evaluate the anti-nociceptive activity, the acetic acid-induced abdominal writhing test, tail flick test and formalin-induced pain test were used. The anti-inflammatory activity was evaluated using the models of paw oedema and pleurisy induced by carrageenan and some inflammatory parameters were evaluated, including cell migration, myeloperoxidase enzyme activity and the levels of TNF-α and IL-1β cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay. LQFM182 (50, 100 or 200 mg/kg, p.o.) decreased the number of writhings induced by acetic acid in a dose-dependent manner, and an intermediate dose (100 mg/kg, p.o.) reduced the paw licking time of animals in the second phase of the formalin test. Furthermore, LQFM182 (100 mg/kg, p.o.) reduced oedema formation at all hours of the paw oedema induced by carrageenan test and in pleurisy test reduced cell migration from the reduction of polymorphonuclear cells, myeloperoxidase enzyme activity and the levels of pro-inflammatory cytokines IL-1β and TNF-α. Therefore, it was classified in GHS category 300 < LD50 < 2000 mg/kg. Reduction of the TNF-α and IL-1β levels.

  • anti nociceptive and anti inflammatory activities of 4 1 phenyl 1h pyrazol 4 yl methyl 1 Piperazine carboxylic acid ethyl ester a new Piperazine Derivative
    Pharmacology Biochemistry and Behavior, 2015
    Co-Authors: Daiany P B Silva, Ricardo Menegatti, Iziara F Florentino, Lanussy Porfiro De Oliveira, Roberta Campos Lino, Pablinny M Galdino, Elson Alves Costa
    Abstract:

    Abstract Piperazine compounds possess anti-infective, anti-carcinogenic, anxiolytic, hypotensive, anti-hypertensive and vasorelaxant properties and are attractive candidates for the development of new analgesic and anti-inflammatory drugs. This study investigates the anti-nociceptive and anti-inflammatory effects of Piperazine Derivative 4-[(1-phenyl-1H-pyrazol-4-yl) methyl]1-Piperazine carboxylic acid ethyl ester (LQFM-008) and the involvement of the serotonergic pathway. In the formalin test, treatments with LQFM-008 (15 and 30 mg/kg p.o.) reduced the licking time in both neurogenic and inflammatory phases of this test. In the tail flick and hot plate tests, LQFM008 treatment (15 and 30 mg/kg p.o.) increased latency to thermal stimulus, suggesting the involvement of central mechanisms in the anti-nociceptive effect of LQFM-008. In the carrageenan-induced paw edema test, LQFM-008 (p.o.) at the doses of 15 and 30 mg/kg reduced the edema at all tested time points, while the dose of 7.5 mg/kg reduced the edema only for the first hour. LQFM-008 (30 mg/kg p.o.) reduced both cell migration and protein exudation in the carrageenan-induced pleurisy test. Furthermore, pre-treatment with NAN-190 (0.6 mg/kg i.p.) and PCPA (100 mg/kg i.p.) antagonized the anti-nociceptive effect of LQFM-008 in both phases of the formalin test. Our data suggest that LQFM-008 possesses anti-inflammatory and anti-nociceptive effects mediated through the serotonergic pathway.

  • hypotensive and antihypertensive potential of 4 1 phenyl 1h pyrazol 4 yl methyl 1 Piperazine carboxylic acid ethyl ester a Piperazine Derivative
    Life Sciences, 2014
    Co-Authors: James Oluwagbamigbe Fajemiroye, Elson Alves Costa, Pablinny M Galdino, Nathalia Oda Amaral, Elaine Fernanda Da Silva, Thiago Sardinha De Oliveira, Paulo Cesar Ghedini, Jordan K Zjawiony, Gustavo Rodrigues Pedrino, Ricardo Menegatti
    Abstract:

    Abstract Aims Clinical complaints on the first-line of cardiovascular medications make continuous search for new drugs a necessity. This study evaluated the cardiovascular effects and mechanism of 4-[(1-phenyl-1 H -pyrazol-4-yl)methyl]1-Piperazine carboxylic acid ethyl ester (LQFM008). Main methods Normotensive male Wistar or spontaneously hypertensive rats (anesthetized or conscious) were used to evaluate the effect of LQFM008 on the mean arterial pressure (MAP), heart rate (HR), arterial blood flow (ABF), arterial vascular conductance (AVC), baroreflex effectiveness index (BI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and vascular function. Key findings In anesthetized normotensive rats, LQFM008 (7.3, 14.3 or 28.6 μmol/kg, iv) reduced MAP (− 21.1 ± 2.7; − 23.9 ± 4.7 or − 32.4 ± 8.3 mm Hg, respectively) and AVC (22%, 32% or 38%) in a dose-dependent manner. LQFM008 elicited a temporal reduction in the SBP and DBP without changes to the BI of conscious normotensive rats. In hypertensive rats, LQFM008 (7.3, 14.3 or 28.6 μmol/kg, iv) reduced MAP ( −2.3 ± 2.6; − 29.3 ± 2.7 or  −38.4 ± 2.8 mmHg, respectively) and increased HR (1.6 ± 3.7; 15.4 ± 4.9 or 25.5 ± 6.2 bmp, respectively) in a dose-dependent manner. A week of oral administration of LQFM008 47.7 μmol/kg elicited a temporal reduction in SBP of hypertensive rats. Pretreatments with atropine, WAY-100635 or L-NAME blocked the effect of LQFM008. In addition, LQFM008-induced endothelium-dependent vascular relaxation was inhibited by L-NAME. Significance Our findings showed hypotensive, antihypertensive and vasorelaxant effects of LQFM008 and suggest the participation of nitric oxide, 5-HT1A and muscarinic receptors.

  • central pharmacological activity of a new Piperazine Derivative 4 1 phenyl 1h pyrazol 4 ylmethyl Piperazine 1 carboxylic acid ethyl ester
    Life Sciences, 2012
    Co-Authors: Adriane Ferreira De Brito, Ricardo Menegatti, Pablinny M Galdino, Jose Luis Rodrigues Martins, James Oluwagbamigbe Fajemiroye, Thereza C M De Lima, Elson Alves Costa
    Abstract:

    Abstract Aims Our study focuses on the design and synthesis of a new piperazinic derivate, 4-(1-phenyl-1h-Pyrazol-4-Ylmethyl)-Piperazine-1-Carboxylic Acid Ethyl ester (LQFM008), and evaluation of its anxiolytic-like profile in Swiss mice. Main methods LQFM008 was evaluated in a screening test of the central nervous system including the rota-rod, sodium pentobarbital-induced sleep, open field, elevated plus maze and light–dark box tests. Key findings LQFM008 induced convulsions at the dose of 1.1 mmol/kg (i.p., s.c. or p.o.). LQFM008 up to 400 μmol/kg had no effect in the rota rod test. In the open field test, LQFM008 increased the number of crossings and the time spent at the central area as well as the sleeping time in sodium pentobarbital-induced sleep. In the elevated plus maze and light–dark box tests, this compound showed an anxiolytic-like activity. This anxiolytic-like activity was antagonized by NAN-190 (5-HT1A antagonist) but not by flumazenil (benzodiazepine antagonist). Significance The compound LQFM008 showed anxiolytic-like activity which may involve serotonergic pathway.

Ricardo Menegatti - One of the best experts on this subject based on the ideXlab platform.

  • neuropharmacological assessment in mice and molecular docking of Piperazine Derivative lqfm212
    Behavioural Brain Research, 2020
    Co-Authors: Lorrane Kelle Da Silva Moreira, Adriane Ferreira De Brito, Crisciele Fontana, Flavio Souza De Carvalho, German Sanz, Luciano M Liao, Fabio Fagundes Da Rocha, Hugo Verli, Ricardo Menegatti, Elson Alves Costa
    Abstract:

    Abstract Piperazine Derivatives are an attractive class of chemical compounds for the treatment of various mental illness. Herein, we demonstrated the synthesis of LQFM212, a Piperazine Derivative, behavioral evaluation in mice and computational studies. In neuropharmacological assessment, LQFM212 treatment at doses of 18, 54 or 162 μmol/kg increased the sleep duration in sodium pentobarbital-induced sleep test. LQFM212 at dose of 162 μmol/kg increased climbing time in the chimney test and decreased the number of squares crossed in the open field test, suggesting that LQFM212 in high doses reduces spontaneous movement. However, LQFM212 treatment at the doses of 18 or 54 μmol/kg increased the preference for the center of field which could be indicative of anxiolytic-like effects. In elevated plus maze and light-dark box tests, LQFM212 treatment altered all parameters observed that demonstrate anxiolytic-like activity. These effects were reversed by flumazenil, mecamylamine, WAY-100635 and PCPA, but not with ketanserin, showing that anxiolytic-like activity involve benzodiazepine site of GABAA receptor, nicotinic and serotonergic pathways. Molecular docking of LQFM212 showed that the ligand has more interactions with GABAA receptor than with 5-HT1A receptor. Despite the involvement of benzodiazepine site on anxiolytic-like effect of LQFM212, treatment with this compound did not alter cognitive function in the step-down avoidance test. In this sense, this Piperazine Derivative is a good prototype for treating anxiety disorders with putative mechanism of action.

  • anti inflammatory effect of a new Piperazine Derivative 4 methylpiperazin 1 yl 1 phenyl 1h pyrazol 4 yl methanone
    Inflammopharmacology, 2018
    Co-Authors: Daniel Da Costa Batista, German Sanz, Luciano M Liao, Elson Alves Costa, Daiany P B Silva, Iziara F Florentino, Carina Sofia Cardoso, Merita P Goncalves, Marize Campos Valadares, Ricardo Menegatti
    Abstract:

    This study investigates the anti-nociceptive and anti-inflammatory effects of new Piperazine compound (LQFM182) as well as the toxicity acute in vitro. To evaluate the anti-nociceptive activity, the acetic acid-induced abdominal writhing test, tail flick test and formalin-induced pain test were used. The anti-inflammatory activity was evaluated using the models of paw oedema and pleurisy induced by carrageenan and some inflammatory parameters were evaluated, including cell migration, myeloperoxidase enzyme activity and the levels of TNF-α and IL-1β cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay. LQFM182 (50, 100 or 200 mg/kg, p.o.) decreased the number of writhings induced by acetic acid in a dose-dependent manner, and an intermediate dose (100 mg/kg, p.o.) reduced the paw licking time of animals in the second phase of the formalin test. Furthermore, LQFM182 (100 mg/kg, p.o.) reduced oedema formation at all hours of the paw oedema induced by carrageenan test and in pleurisy test reduced cell migration from the reduction of polymorphonuclear cells, myeloperoxidase enzyme activity and the levels of pro-inflammatory cytokines IL-1β and TNF-α. Therefore, it was classified in GHS category 300 < LD50 < 2000 mg/kg. Reduction of the TNF-α and IL-1β levels.

  • anti nociceptive and anti inflammatory activities of 4 1 phenyl 1h pyrazol 4 yl methyl 1 Piperazine carboxylic acid ethyl ester a new Piperazine Derivative
    Pharmacology Biochemistry and Behavior, 2015
    Co-Authors: Daiany P B Silva, Ricardo Menegatti, Iziara F Florentino, Lanussy Porfiro De Oliveira, Roberta Campos Lino, Pablinny M Galdino, Elson Alves Costa
    Abstract:

    Abstract Piperazine compounds possess anti-infective, anti-carcinogenic, anxiolytic, hypotensive, anti-hypertensive and vasorelaxant properties and are attractive candidates for the development of new analgesic and anti-inflammatory drugs. This study investigates the anti-nociceptive and anti-inflammatory effects of Piperazine Derivative 4-[(1-phenyl-1H-pyrazol-4-yl) methyl]1-Piperazine carboxylic acid ethyl ester (LQFM-008) and the involvement of the serotonergic pathway. In the formalin test, treatments with LQFM-008 (15 and 30 mg/kg p.o.) reduced the licking time in both neurogenic and inflammatory phases of this test. In the tail flick and hot plate tests, LQFM008 treatment (15 and 30 mg/kg p.o.) increased latency to thermal stimulus, suggesting the involvement of central mechanisms in the anti-nociceptive effect of LQFM-008. In the carrageenan-induced paw edema test, LQFM-008 (p.o.) at the doses of 15 and 30 mg/kg reduced the edema at all tested time points, while the dose of 7.5 mg/kg reduced the edema only for the first hour. LQFM-008 (30 mg/kg p.o.) reduced both cell migration and protein exudation in the carrageenan-induced pleurisy test. Furthermore, pre-treatment with NAN-190 (0.6 mg/kg i.p.) and PCPA (100 mg/kg i.p.) antagonized the anti-nociceptive effect of LQFM-008 in both phases of the formalin test. Our data suggest that LQFM-008 possesses anti-inflammatory and anti-nociceptive effects mediated through the serotonergic pathway.

  • hypotensive and antihypertensive potential of 4 1 phenyl 1h pyrazol 4 yl methyl 1 Piperazine carboxylic acid ethyl ester a Piperazine Derivative
    Life Sciences, 2014
    Co-Authors: James Oluwagbamigbe Fajemiroye, Elson Alves Costa, Pablinny M Galdino, Nathalia Oda Amaral, Elaine Fernanda Da Silva, Thiago Sardinha De Oliveira, Paulo Cesar Ghedini, Jordan K Zjawiony, Gustavo Rodrigues Pedrino, Ricardo Menegatti
    Abstract:

    Abstract Aims Clinical complaints on the first-line of cardiovascular medications make continuous search for new drugs a necessity. This study evaluated the cardiovascular effects and mechanism of 4-[(1-phenyl-1 H -pyrazol-4-yl)methyl]1-Piperazine carboxylic acid ethyl ester (LQFM008). Main methods Normotensive male Wistar or spontaneously hypertensive rats (anesthetized or conscious) were used to evaluate the effect of LQFM008 on the mean arterial pressure (MAP), heart rate (HR), arterial blood flow (ABF), arterial vascular conductance (AVC), baroreflex effectiveness index (BI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and vascular function. Key findings In anesthetized normotensive rats, LQFM008 (7.3, 14.3 or 28.6 μmol/kg, iv) reduced MAP (− 21.1 ± 2.7; − 23.9 ± 4.7 or − 32.4 ± 8.3 mm Hg, respectively) and AVC (22%, 32% or 38%) in a dose-dependent manner. LQFM008 elicited a temporal reduction in the SBP and DBP without changes to the BI of conscious normotensive rats. In hypertensive rats, LQFM008 (7.3, 14.3 or 28.6 μmol/kg, iv) reduced MAP ( −2.3 ± 2.6; − 29.3 ± 2.7 or  −38.4 ± 2.8 mmHg, respectively) and increased HR (1.6 ± 3.7; 15.4 ± 4.9 or 25.5 ± 6.2 bmp, respectively) in a dose-dependent manner. A week of oral administration of LQFM008 47.7 μmol/kg elicited a temporal reduction in SBP of hypertensive rats. Pretreatments with atropine, WAY-100635 or L-NAME blocked the effect of LQFM008. In addition, LQFM008-induced endothelium-dependent vascular relaxation was inhibited by L-NAME. Significance Our findings showed hypotensive, antihypertensive and vasorelaxant effects of LQFM008 and suggest the participation of nitric oxide, 5-HT1A and muscarinic receptors.

  • central pharmacological activity of a new Piperazine Derivative 4 1 phenyl 1h pyrazol 4 ylmethyl Piperazine 1 carboxylic acid ethyl ester
    Life Sciences, 2012
    Co-Authors: Adriane Ferreira De Brito, Ricardo Menegatti, Pablinny M Galdino, Jose Luis Rodrigues Martins, James Oluwagbamigbe Fajemiroye, Thereza C M De Lima, Elson Alves Costa
    Abstract:

    Abstract Aims Our study focuses on the design and synthesis of a new piperazinic derivate, 4-(1-phenyl-1h-Pyrazol-4-Ylmethyl)-Piperazine-1-Carboxylic Acid Ethyl ester (LQFM008), and evaluation of its anxiolytic-like profile in Swiss mice. Main methods LQFM008 was evaluated in a screening test of the central nervous system including the rota-rod, sodium pentobarbital-induced sleep, open field, elevated plus maze and light–dark box tests. Key findings LQFM008 induced convulsions at the dose of 1.1 mmol/kg (i.p., s.c. or p.o.). LQFM008 up to 400 μmol/kg had no effect in the rota rod test. In the open field test, LQFM008 increased the number of crossings and the time spent at the central area as well as the sleeping time in sodium pentobarbital-induced sleep. In the elevated plus maze and light–dark box tests, this compound showed an anxiolytic-like activity. This anxiolytic-like activity was antagonized by NAN-190 (5-HT1A antagonist) but not by flumazenil (benzodiazepine antagonist). Significance The compound LQFM008 showed anxiolytic-like activity which may involve serotonergic pathway.

Daiany P B Silva - One of the best experts on this subject based on the ideXlab platform.

  • 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
    Biomedicine & Pharmacotherapy, 2018
    Co-Authors: Dayane Moreira Da Silva, Lorrane Kelle Da Silva Moreira, Adriane Ferreira De Brito, German Sanz, Luciano M Liao, Daiany P B Silva, Carina Sofia Cardoso, Flavio Silva De Carvalho, Danillo Ramos De Oliveira, Fabio Fagundes Da Rocha
    Abstract:

    Abstract 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.

  • 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
    Naunyn-Schmiedeberg's Archives of Pharmacology, 2018
    Co-Authors: Adriane F. Brito, German Sanz, Luciano M Liao, Daiany P B Silva, Patrícia C. C. S. Braga, Lorrane K. S. Moreira, Dayane M. Silva, Flávio S. Carvalho, Rafaela R. Silva, François Noël
    Abstract:

    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_1B, 5-HT_1A, and D_2 receptors, however, within the low micromolar range. We conclude that LQFM180 should be considered as a scaffold for drug candidate development.

  • anti inflammatory effect of a new Piperazine Derivative 4 methylpiperazin 1 yl 1 phenyl 1h pyrazol 4 yl methanone
    Inflammopharmacology, 2018
    Co-Authors: Daniel Da Costa Batista, German Sanz, Luciano M Liao, Elson Alves Costa, Daiany P B Silva, Iziara F Florentino, Carina Sofia Cardoso, Merita P Goncalves, Marize Campos Valadares, Ricardo Menegatti
    Abstract:

    This study investigates the anti-nociceptive and anti-inflammatory effects of new Piperazine compound (LQFM182) as well as the toxicity acute in vitro. To evaluate the anti-nociceptive activity, the acetic acid-induced abdominal writhing test, tail flick test and formalin-induced pain test were used. The anti-inflammatory activity was evaluated using the models of paw oedema and pleurisy induced by carrageenan and some inflammatory parameters were evaluated, including cell migration, myeloperoxidase enzyme activity and the levels of TNF-α and IL-1β cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay. LQFM182 (50, 100 or 200 mg/kg, p.o.) decreased the number of writhings induced by acetic acid in a dose-dependent manner, and an intermediate dose (100 mg/kg, p.o.) reduced the paw licking time of animals in the second phase of the formalin test. Furthermore, LQFM182 (100 mg/kg, p.o.) reduced oedema formation at all hours of the paw oedema induced by carrageenan test and in pleurisy test reduced cell migration from the reduction of polymorphonuclear cells, myeloperoxidase enzyme activity and the levels of pro-inflammatory cytokines IL-1β and TNF-α. Therefore, it was classified in GHS category 300 < LD50 < 2000 mg/kg. Reduction of the TNF-α and IL-1β levels.

  • anti nociceptive and anti inflammatory activities of 4 1 phenyl 1h pyrazol 4 yl methyl 1 Piperazine carboxylic acid ethyl ester a new Piperazine Derivative
    Pharmacology Biochemistry and Behavior, 2015
    Co-Authors: Daiany P B Silva, Ricardo Menegatti, Iziara F Florentino, Lanussy Porfiro De Oliveira, Roberta Campos Lino, Pablinny M Galdino, Elson Alves Costa
    Abstract:

    Abstract Piperazine compounds possess anti-infective, anti-carcinogenic, anxiolytic, hypotensive, anti-hypertensive and vasorelaxant properties and are attractive candidates for the development of new analgesic and anti-inflammatory drugs. This study investigates the anti-nociceptive and anti-inflammatory effects of Piperazine Derivative 4-[(1-phenyl-1H-pyrazol-4-yl) methyl]1-Piperazine carboxylic acid ethyl ester (LQFM-008) and the involvement of the serotonergic pathway. In the formalin test, treatments with LQFM-008 (15 and 30 mg/kg p.o.) reduced the licking time in both neurogenic and inflammatory phases of this test. In the tail flick and hot plate tests, LQFM008 treatment (15 and 30 mg/kg p.o.) increased latency to thermal stimulus, suggesting the involvement of central mechanisms in the anti-nociceptive effect of LQFM-008. In the carrageenan-induced paw edema test, LQFM-008 (p.o.) at the doses of 15 and 30 mg/kg reduced the edema at all tested time points, while the dose of 7.5 mg/kg reduced the edema only for the first hour. LQFM-008 (30 mg/kg p.o.) reduced both cell migration and protein exudation in the carrageenan-induced pleurisy test. Furthermore, pre-treatment with NAN-190 (0.6 mg/kg i.p.) and PCPA (100 mg/kg i.p.) antagonized the anti-nociceptive effect of LQFM-008 in both phases of the formalin test. Our data suggest that LQFM-008 possesses anti-inflammatory and anti-nociceptive effects mediated through the serotonergic pathway.

Manisha Tiwari - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacological evaluation of novel 1-[4-(4-benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-phenyl]-3-phenyl-urea as potent anticonvulsant and antidepressant agent
    Pharmacological Reports, 2016
    Co-Authors: Shikha Kumari, Chandra Bhushan Mishra, Manisha Tiwari
    Abstract:

    Background Earlier, we have identified a number of Piperazine Derivatives having good anticonvulsant activity in vivo and as a part of our ongoing search for potent anticonvulsant agent, we herein describes the synthesis of an aryl Piperazine Derivative “1-[4-(4-benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-phenyl]-3-phenyl-urea” (BPPU). The anticonvulsant and antidepressant activity of BPPU was checked in various in vivo models. Methods Anticonvulsant activity was assessed in maximal electroshock test (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure tests. Moreover, plausible mechanistic studies were also performed by using several chemical induced seizure models. The antidepressant activity of BPPU was checked in forced swim test (FST) and tail suspension test (TST) in mice. Drug safety profile was studied in sub-acute toxicity rat model at a dose of 100 mg/kg, per oral for 14 days. Results BPPU exhibited excellent protection against seizures induced by MES and scPTZ in mice as well as rats. In pilocarpine induced model of status epilepticus (SE), BPPU demonstrated 50% protection at a dose of 100 mg/kg in rats. BPPU also successfully inhibited seizures induced by 3-mercaptopropionic acid (3-MPA) and thiosemicarbazide (TSC) in mice thus, suggested that BPPU might influence GABA-ergic neurotransmission in the brain. Moreover, BPPU showed good antidepressant activity and did not exhibit any significant toxicity. Conclusion BPPU displayed broad spectrum of anticonvulsant activity in several seizure models along with satisfactory antidepressant activity. Therefore, BPPU may be further developed as a potential therapeutic agent for therapy of epileptic disorders.

  • protective effects of a Piperazine Derivative n 4 4 2 methoxy phenyl piperazin 1 yl phenyl carbamic acid ethyl ester against aluminium induced neurotoxicity insights from in silico and in vivo studies
    Neurotoxicity Research, 2015
    Co-Authors: Poonam Meena, Apra Manral, Vikas Saini, Manisha Tiwari
    Abstract:

    The cholinergic hypothesis associated with Alzheimer’s disease has spurred the development of numerous structural classes of compounds with different pharmacological profiles aimed at increasing central cholinergic neurotransmission. In the present study, six synthetic Piperazine Derivatives D1–D6 were screened for their efficacy as acetylcholinesterase inhibitors (AChEIs) through in silico and in vitro studies. Compound D2 was found to be a potential AChEI with adequate pharmacokinetic properties, as supported by in silico study. Further, in vivo studies were designed to examine the protective effect of Piperazine Derivative D2 (3 and 5 mg/kg for 6 weeks) in ameliorating the alterations induced by aluminium chloride (AlCl3) on behavioural and neurochemical indices. Behavioural tests (Morris water maze and elevated plus maze) revealed significant alterations in the short-term memory and anxiety levels in rats treated with AlCl3, which was further improved after D2 treatment. Further, D2 treatment attenuated the neurotoxic effects of AlCl3 as shown by the improvement in rats performance in Water maze test and in lowering AChE activity. Besides preventing lipid peroxidation and protein damage, changes in the levels of endogenous antioxidant enzymes (GST, GPx, GR and GSH) associated with AlCl3 administration were also restored upon treatment with D2. Thus, our results support the neuroprotective potential of compound D2, thus validating its use in alleviating toxic effects of aluminium.

Pablinny M Galdino - One of the best experts on this subject based on the ideXlab platform.

  • anti nociceptive and anti inflammatory activities of 4 1 phenyl 1h pyrazol 4 yl methyl 1 Piperazine carboxylic acid ethyl ester a new Piperazine Derivative
    Pharmacology Biochemistry and Behavior, 2015
    Co-Authors: Daiany P B Silva, Ricardo Menegatti, Iziara F Florentino, Lanussy Porfiro De Oliveira, Roberta Campos Lino, Pablinny M Galdino, Elson Alves Costa
    Abstract:

    Abstract Piperazine compounds possess anti-infective, anti-carcinogenic, anxiolytic, hypotensive, anti-hypertensive and vasorelaxant properties and are attractive candidates for the development of new analgesic and anti-inflammatory drugs. This study investigates the anti-nociceptive and anti-inflammatory effects of Piperazine Derivative 4-[(1-phenyl-1H-pyrazol-4-yl) methyl]1-Piperazine carboxylic acid ethyl ester (LQFM-008) and the involvement of the serotonergic pathway. In the formalin test, treatments with LQFM-008 (15 and 30 mg/kg p.o.) reduced the licking time in both neurogenic and inflammatory phases of this test. In the tail flick and hot plate tests, LQFM008 treatment (15 and 30 mg/kg p.o.) increased latency to thermal stimulus, suggesting the involvement of central mechanisms in the anti-nociceptive effect of LQFM-008. In the carrageenan-induced paw edema test, LQFM-008 (p.o.) at the doses of 15 and 30 mg/kg reduced the edema at all tested time points, while the dose of 7.5 mg/kg reduced the edema only for the first hour. LQFM-008 (30 mg/kg p.o.) reduced both cell migration and protein exudation in the carrageenan-induced pleurisy test. Furthermore, pre-treatment with NAN-190 (0.6 mg/kg i.p.) and PCPA (100 mg/kg i.p.) antagonized the anti-nociceptive effect of LQFM-008 in both phases of the formalin test. Our data suggest that LQFM-008 possesses anti-inflammatory and anti-nociceptive effects mediated through the serotonergic pathway.

  • hypotensive and antihypertensive potential of 4 1 phenyl 1h pyrazol 4 yl methyl 1 Piperazine carboxylic acid ethyl ester a Piperazine Derivative
    Life Sciences, 2014
    Co-Authors: James Oluwagbamigbe Fajemiroye, Elson Alves Costa, Pablinny M Galdino, Nathalia Oda Amaral, Elaine Fernanda Da Silva, Thiago Sardinha De Oliveira, Paulo Cesar Ghedini, Jordan K Zjawiony, Gustavo Rodrigues Pedrino, Ricardo Menegatti
    Abstract:

    Abstract Aims Clinical complaints on the first-line of cardiovascular medications make continuous search for new drugs a necessity. This study evaluated the cardiovascular effects and mechanism of 4-[(1-phenyl-1 H -pyrazol-4-yl)methyl]1-Piperazine carboxylic acid ethyl ester (LQFM008). Main methods Normotensive male Wistar or spontaneously hypertensive rats (anesthetized or conscious) were used to evaluate the effect of LQFM008 on the mean arterial pressure (MAP), heart rate (HR), arterial blood flow (ABF), arterial vascular conductance (AVC), baroreflex effectiveness index (BI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and vascular function. Key findings In anesthetized normotensive rats, LQFM008 (7.3, 14.3 or 28.6 μmol/kg, iv) reduced MAP (− 21.1 ± 2.7; − 23.9 ± 4.7 or − 32.4 ± 8.3 mm Hg, respectively) and AVC (22%, 32% or 38%) in a dose-dependent manner. LQFM008 elicited a temporal reduction in the SBP and DBP without changes to the BI of conscious normotensive rats. In hypertensive rats, LQFM008 (7.3, 14.3 or 28.6 μmol/kg, iv) reduced MAP ( −2.3 ± 2.6; − 29.3 ± 2.7 or  −38.4 ± 2.8 mmHg, respectively) and increased HR (1.6 ± 3.7; 15.4 ± 4.9 or 25.5 ± 6.2 bmp, respectively) in a dose-dependent manner. A week of oral administration of LQFM008 47.7 μmol/kg elicited a temporal reduction in SBP of hypertensive rats. Pretreatments with atropine, WAY-100635 or L-NAME blocked the effect of LQFM008. In addition, LQFM008-induced endothelium-dependent vascular relaxation was inhibited by L-NAME. Significance Our findings showed hypotensive, antihypertensive and vasorelaxant effects of LQFM008 and suggest the participation of nitric oxide, 5-HT1A and muscarinic receptors.

  • central pharmacological activity of a new Piperazine Derivative 4 1 phenyl 1h pyrazol 4 ylmethyl Piperazine 1 carboxylic acid ethyl ester
    Life Sciences, 2012
    Co-Authors: Adriane Ferreira De Brito, Ricardo Menegatti, Pablinny M Galdino, Jose Luis Rodrigues Martins, James Oluwagbamigbe Fajemiroye, Thereza C M De Lima, Elson Alves Costa
    Abstract:

    Abstract Aims Our study focuses on the design and synthesis of a new piperazinic derivate, 4-(1-phenyl-1h-Pyrazol-4-Ylmethyl)-Piperazine-1-Carboxylic Acid Ethyl ester (LQFM008), and evaluation of its anxiolytic-like profile in Swiss mice. Main methods LQFM008 was evaluated in a screening test of the central nervous system including the rota-rod, sodium pentobarbital-induced sleep, open field, elevated plus maze and light–dark box tests. Key findings LQFM008 induced convulsions at the dose of 1.1 mmol/kg (i.p., s.c. or p.o.). LQFM008 up to 400 μmol/kg had no effect in the rota rod test. In the open field test, LQFM008 increased the number of crossings and the time spent at the central area as well as the sleeping time in sodium pentobarbital-induced sleep. In the elevated plus maze and light–dark box tests, this compound showed an anxiolytic-like activity. This anxiolytic-like activity was antagonized by NAN-190 (5-HT1A antagonist) but not by flumazenil (benzodiazepine antagonist). Significance The compound LQFM008 showed anxiolytic-like activity which may involve serotonergic pathway.