16 results on '"Rates, Stela M.K."'
Search Results
2. Determination of pharmacological interactions of uliginosin B, a natural phloroglucinol derivative, with amitriptyline, clonidine and morphine by isobolographic analysis.
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Stolz, Eveline D., Müller, Liz G., Antonio, Camila B., da Costa, Paola F., von Poser, Gilsane L., Noël, François, and Rates, Stela M.K.
- Abstract
Uliginosin B is a natural phloroglucinol derivative, obtained from Hypericum species native to South America. Previous studies have shown that uliginosin B presents antidepressant-like and antinociceptive effects. Although its mechanism of action is still not completely elucidated, it is known that it involves the activation of monoaminergic neurotransmission. The aim of the current study was to further investigate the antinociceptive mechanism of action of uliginosin B by combining it with different drugs used for treating pain in clinical practice. The intraperitoneal administration of uliginosin B, morphine, amitriptyline and clonidine, alone or in mixture, produced a dose-dependent antinociceptive effect in the hot-plate assay in mice. The effect of the mixtures of drugs was studied using an adapted isobologram analysis at the effect level of 50% of the maximal effect observed. The analysis showed that the interactions between uliginosin B and morphine was synergistic, while the interactions between uliginosin B and amitriptyline or clonidine were additive. These findings point to uliginosin B as a potential adjuvant for pain pharmacotherapy, especially for opioid analgesia. [ABSTRACT FROM AUTHOR]
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- 2014
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3. Dimeric acylphloroglucinols from Hypericum austrobrasiliense exhibiting antinociceptive activity in mice.
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Bridi, Henrique, Ccana-Ccapatinta, Gari V., Stolz, Eveline D., Meirelles, Gabriela C., Bordignon, Sérgio A.L., Rates, Stela M.K., and von Poser, Gilsane L.
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HYPERICUM , *PHLOROGLUCINOL , *ANALGESICS , *LABORATORY mice , *REPRODUCTIVE isolation in plants - Abstract
Three dimeric acylphloroglucinols, austrobrasilol A, austrobrasilol B and isoaustrobrasilol B were isolated from the flowers of Hypericum austrobrasiliense (Hypericaceae, section Trigynobrathys ). Their structures were elucidated using mass spectrometry and NMR experiments (1D and 2D), and by comparison with previously reported data for other dimeric acylphloroglucinols isolated from Hypericum and Elaphoglossum genera. The three compounds were orally administered in mice at equimolar doses to uliginosin B (15 mg/kg, p.o.) displaying antinociceptive activity in the hot-plate test. The compounds did not induce motor impairment in the rotarod apparatus. [ABSTRACT FROM AUTHOR]
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- 2016
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4. Synthesis and pharmacological evaluation of new N-phenylpiperazine derivatives designed as homologues of the antipsychotic lead compound LASSBio-579.
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Pompeu, Thais E.T., Alves, Fernando R.S., Figueiredo, Carolina D.M., Antonio, Camila B., Herzfeldt, Vivian, Moura, Bruna C., Rates, Stela M.K., Barreiro, Eliezer J., Fraga, Carlos A.M., and Noël, François
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PHENYL compounds , *PIPERAZINE , *ANTIPSYCHOTIC agents , *LEAD compounds synthesis , *ALPHA adrenoceptors , *SCHIZOPHRENIA treatment , *THERAPEUTICS - Abstract
Abstract: In an attempt to increase the affinity of our antipsychotic lead compound LASSBio-579 (1-((1-(4-chlorophenyl)-1H-pyrazol-4-yl)methyl)-4-phenylpiperazine; (2)) for the 5-HT2A receptor, we synthesized five new N-phenylpiperazine derivatives using a linear synthetic route and the homologation strategy. The binding profile of these compounds was evaluated for a series of dopaminergic, serotonergic and alpha-adrenergic receptors relevant for schizophrenia, using classical competition assays. Increasing the length of the spacer between the functional groups of (2) proved to be appropriated since the affinity of these compounds increased 3–10-fold for the 5-HT2A receptor, with no relevant change in the affinity for the D2-like and 5-HT1A receptors. A GTP-shift assay also indicated that the most promising derivative (1-(4-(1-(4-chlorophenyl)-1H-pyrazol-4-yl) butyl)-4-phenylpiperazine) (LASSBio-1635) (6) has the expected efficacy at the 5-HT2A receptors, acting as an antagonist. Intraperitoneal administration of (6) prevented apomorphine-induced climbing behavior and ketamine-induced hyperlocomotion in mice, in a dose dependent manner. Together, these results show that (6) could be considered as a new antipsychotic lead compound. [Copyright &y& Elsevier]
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- 2013
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5. Biotransformation of LASSBio-579 and pharmacological evaluation of p-hydroxylated metabolite a N-phenylpiperazine antipsychotic lead compound
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Gomes, Tatiana F., Pompeu, Thais E.T., Rodrigues, Daniel A., Noël, François, Menegatti, Ricardo, Andrade, Carolina H., Sabino, José R., Gil, Eric S., Dalla Costa, Teresa, Betti, Andresa H., Antonio, Camila B., Rates, Stela M.K., Fraga, Carlos A.M., Barreiro, Eliezer J., and de Oliveira, Valéria
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BIOTRANSFORMATION (Metabolism) , *HYDROXYLATION , *METABOLITE synthesis , *PIPERAZINE , *ANTIPSYCHOTIC agents , *LEAD compounds , *DRUG development , *THERAPEUTICS - Abstract
Abstract: Using a combination of docking and molecular dynamics simulations, we predicted that p-hydroxylation by CYP1A2 would be the main metabolic pathway for the 1-[1-(4-chlorophenyl)-1H-4pyrazolylmethyl] phenylhexahydropiperazine, LASSBio-579 (3). As the result of a screening process with strains of filamentous fungi, Cunninghamella echinulata ATCC 9244 was chosen to scale up the preparation of the p-hydroxylated metabolite (4). About 30 min after i.p. administration of (3) to rats was identified as the p-hydroxylated metabolite, confirming our in silico previsions. Chemical synthesis of the metabolite was performed and allowed its pharmacological evaluation in binding assays revealing its high affinity for D2 and D4 receptors, indicating that this metabolite should participate to the antipsychotic effect of (3) in vivo. Furthermore, we report here that both (3) and its p-hydroxylated metabolite (4) have a much lower affinity than clozapine for two receptors involved in adverse reactions. Voltammetric assays were useful to understand the redox profile of (3). [Copyright &y& Elsevier]
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- 2013
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6. New insights into pharmacological profile of LASSBio-579, a multi-target N-phenylpiperazine derivative active on animal models of schizophrenia
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Neves, Gilda, Antonio, Camila B., Betti, Andresa H., Pranke, Mariana A., Fraga, Carlos A.M., Barreiro, Eliezer J., Noël, François, and Rates, Stela M.K.
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SCHIZOPHRENIA treatment , *PHARMACOLOGY , *PIPERAZINE , *PHENYL compounds , *DRUG derivatives , *ANTIPSYCHOTIC agents , *MEDICAL statistics - Abstract
Abstract: Previous behavioral and receptor binding studies on N-phenylpiperazine derivatives by our group indicated that LASSBio-579, LASSBio-580 and LASSBio-581 could be potential antipsychotic lead compounds. The present study identified LASSBio-579 as the most promising among the three compounds, since it was the only one that inhibited apomorphine-induced climbing (5mg/kg p.o.) and apomorphine-induced hypothermia (15mg/kg p.o.). Furthermore, LASSBio-579 (0.5mg/kg p.o.) was effective in the ketamine-induced hyperlocomotion test and prevented the prepulse inhibition deficits induced by apomorphine, DOI and ketamine with different potencies (1mg/kg, 0.5mg/kg and 5mg/kg p.o., respectively). LASSBio-579 also induced a motor impairment, catalepsy and a mild sedative effect but only at doses 3–120 times higher than those with antipsychotic-like effects. In addition, LASSBio-579 (0.5 and 1mg/kg p.o.) reversed the catalepsy induced by WAY 100,635, corroborating its action on both dopaminergic and serotonergic neurotransmission and pointing to the contribution of 5-HT1A receptor activation to its pharmacological profile. Moreover, co-administration of sub-effective doses of LASSBio-579 with sub-effective doses of clozapine or haloperidol prevented the apomorphine-induced climbing without induction of catalepsy. In summary, our results characterize LASSBio-579 as a multi-target ligand active in pharmacological animal models of schizophrenia, confirming that this compound could be included in development programs aiming at a new drug for treating schizophrenia. [Copyright &y& Elsevier]
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- 2013
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7. In vivo evaluation of the highly soluble oral β-cyclodextrin–Sertraline supramolecular complexes
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Passos, Joel J., De Sousa, Frederico B., Mundim, Iram M., Bonfim, Ricardo R., Melo, Robson, Viana, Alice F., Stolz, Eveline D., Borsoi, Milene, Rates, Stela M.K., and Sinisterra, Rubén D.
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ORAL drug administration , *DRUG solubility , *CYCLODEXTRINS , *SERTRALINE , *ANTIDEPRESSANTS , *BLOOD plasma , *MOLECULAR structure - Abstract
Abstract: The aim of the present work was to evaluate the antidepressant like-effect and plasma concentration of Sertraline (SRT) using an inclusion complex (IC) with β-cyclodextrin (βCD) in mice. This supramolecular system was prepared using two different molar ratios at 1:1 and 1:2 SRT:βCD and both were characterized to assess the drug inclusion into the host cavity. Based on the X-ray powder diffraction, Fourier transform infrared spectroscopy and thermal analysis the interaction between host and guest molecules could be suggested. This result indicates that the freeze drying process was efficient to prepare the ICs, when these are compared with the physical mixtures. By comparing the solid state results of 1:1 and 1:2 ICs no significant chemical or structural changes were identified between these systems. However, in vivo experiments indicated that the host–guest ratio was able to modify the SRT activity. Mice treated with both ICs (20mgkg−1, p.o.) have shown lower immobility time in the tail suspension test in comparison with mice treated with free SRT (20mgkg−1, p.o.). Mice spontaneous locomotor activity was not affected by any treatment. Higher SRT plasma concentration was determined after 30min of treatment with 1:1 IC in comparison with free SRT, demonstrating the IC greater drug transport efficacy. [Copyright &y& Elsevier]
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- 2012
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8. Uliginosin B presents antinociceptive effect mediated by dopaminergic and opioid systems in mice
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Stolz, Eveline Dischkaln, Viana, Alice Fialho, Hasse, Diego Rafael, von Poser, Gilsane Lino, do Rego, Jean-Claude, and Rates, Stela M.K.
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ANALGESICS , *DOPAMINERGIC mechanisms , *OPIOIDS , *LABORATORY mice , *PHLOROGLUCINOL derivatives , *MAGNETIC resonance imaging of the brain , *HIGH performance liquid chromatography , *GUANOSINE diphosphate - Abstract
Abstract: Previous studies have shown that uliginosin B inhibits dopamine reuptake in rat brain. This compound occurs in Hypericum polyanthemum and H. caprifoliatum for which was reported to have antinociceptive effect sensitive to naloxone. The aim of this study was to assess the antinociceptive effect of uliginosin B and to evaluate the involvement of opioid and dopaminergic receptors activation. Uliginosin B presented antinociceptive effect in hot-plate and abdominal writhing tests, in mice, at doses that did not impair the motor coordination (15mg/kg, i.p.). Uliginosin B in high dose (90mg/kg, i.p.) presented ataxic effect in the rotarod apparatus. These effects seem to be mediated by distinct receptors since the effect on the hot-plate was completely abolished by naloxone and sulpiride, but it was unaffected by SCH 23390. On the other hand, the motor impairment induced by uliginosin B was completely prevented by naloxone and partially prevented by sulpiride and SCH 23390. However, the receptors'' activation appears to be indirect since uliginosin B did not bind to opioid and dopaminergic receptors. Thus, uliginosin B effects probably are due to its ability to inhibit monoamine reuptake with consequent activation of dopamine receptors and indirect stimulation of opioid system. [Copyright &y& Elsevier]
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- 2012
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9. Uliginosin B, a phloroglucinol derivative from Hypericum polyanthemum: A promising new molecular pattern for the development of antidepressant drugs
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Stein, Ana C., Viana, Alice F., Müller, Liz G., Nunes, Jéssica M., Stolz, Eveline D., Do Rego, Jean-Claude, Costentin, Jean, von Poser, Gilsane L., and Rates, Stela M.K.
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PHENOLS , *ANTIDEPRESSANTS , *HYPERICUM , *DRUG development , *CYCLOHEXANE , *PLANT extracts , *LABORATORY rodents - Abstract
Abstract: In this study we have demonstrated that cyclohexane extract of Hypericum polyanthemum (POL) and its main phloroglucinol derivative uliginosin B (ULI) present antidepressant-like activity in rodent forced swimming test (FST). The involvement of monoaminergic neurotransmission on the antidepressant-like activity of ULI was evaluated in vivo and in vitro. POL 90mg/kg (p.o.) and ULI 10mg/kg (p.o.) reduced the immobility time in the mice FST without altering locomotion activity in the open-field test. The combination of sub-effective doses of POL (45mg/kg, p.o.) and ULI (5mg/kg, p.o.) with sub-effective doses of imipramine (10mg/kg, p.o.), bupropion (3mg/kg, p.o.) and fluoxetine (15mg/kg, p.o.) induced a significant reduction on immobility time in FST. The pretreatment with SCH 23390 (15μg/kg, s.c., dopamine D1 receptor antagonist), sulpiride (50mg/kg, i.p., dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., α2-adrenoceptor antagonist) and pCPA (100mg/kg/day, i.p., p-chlorophenilalanine methyl ester, inhibitor of serotonin synthesis, for four consecutive days) before ULI administration (10mg/kg, p.o.) significantly prevented the anti-immobility effect in FST. ULI was able to inhibit synaptosomal uptake of dopamine (IC50 =90±38nM), serotonin (IC50 =252±13nM) and noradrenaline (280±48nM), but it did not bind to any of the monoamine transporters. These data firstly demonstrated the antidepressant-like effect of POL and ULI, which depends on the activation of the monoaminergic neurotransmission in a different manner from the most antidepressants. [Copyright &y& Elsevier]
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- 2012
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10. Antidepressant-like effect of Valeriana glechomifolia Meyer (Valerianaceae) in mice
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Müller, Liz G., Salles, Luisa A., Stein, Ana C., Betti, Andresa H., Sakamoto, Satchie, Cassel, Eduardo, Vargas, Rubem Figueiró, von Poser, Gilsane L., and Rates, Stela M.K.
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ANTIDEPRESSANTS , *VALERIANACEAE , *LABORATORY mice , *LOCOMOTOR control , *PRAZOSIN , *DOPAMINERGIC neurons , *NORADRENERGIC neurons , *NEURAL transmission - Abstract
Abstract: The antidepressant-like effect of a supercritical CO2 (SCCO2) Valeriana glechomifolia extract enriched in valepotriates was investigated in a mice tail suspension test (TST) and forced swimming test (FST). The SCCO2 extract decreased mice immobility in the FST (0.5–20mg/kg p.o.) and elicited a biphasic dose–response relationship in the TST (1–20mg/kg p.o.) with no alterations in locomotor activity and motor coordination (assessed in the open-field and rota-rod tests, respectively). The anti-immobility effect of the SCCO2 extract (5mg/kg, p.o.) was prevented by mice pre-treatment with yohimbine (1mg/kg, i.p., an α2 adrenoceptor antagonist), SCH 23390 (15μg/kg, s.c., D1 dopamine receptor antagonist) and sulpiride (50mg/kg, i.p., D2 dopamine receptor antagonist). However, mice pre-treatments with prazosin (1mg/kg, i.p., α1 adrenoceptor antagonist) and p-chlorophenilalanine methyl ester (4×100mg/kg/day, i.p., a serotonin synthesis inhibitor) were not able to block the anti-immobility effect of the SCCO2 extract. Administration (p.o.) of the SCCO2 extract (0.25mg/kg) and imipramine (10mg/kg), desipramine (5mg/kg) and bupropion (3mg/kg) at sub-effective doses significantly reduced mice immobility time in the FST. These data provide the first evidence of the antidepressant-like activity of V. glechomifolia valepotriates, which is due to an interaction with dopaminergic and noradrenergic neurotransmission. [Copyright &y& Elsevier]
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- 2012
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11. Design of new dopamine D2 receptor ligands: Biosynthesis and pharmacological evaluation of the hydroxylated metabolite of LASSBio-581
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Pazini, Francine, Menegatti, Ricardo, Sabino, José R., Andrade, Carolina H., Neves, Gilda, Rates, Stela M.K., Noël, François, Fraga, Carlos A.M., Barreiro, Eliezer J., and de Oliveira, Valéria
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LIGANDS (Biochemistry) , *DOPAMINE receptors , *BIOSYNTHESIS , *PHARMACOLOGY , *HYDROXYLATION , *METABOLITES , *ANTIPSYCHOTIC agents , *SCHIZOPHRENIA treatment - Abstract
Abstract: LASSBio-581 is a N-phenylpiperazine derivative designed for the treatment of schizophrenia. In this study, four strains of filamentous fungi were screened for their capabilities to biotransform LASSBio-581. Cunninghamella echinulata ATCC 9244 was chosen to scale up the biosynthesis of the p-hydroxylated metabolite of LASSBio-581. The chemical structure of the metabolite was confirmed by NMR, LC–MS and X-ray crystallography. Binding studies performed on brain homogenate indicated that the p-hydroxylated metabolite can be considered more selective for dopamine receptors than LASSBio-581, and, therefore, can be used to design new selective dopamine inhibitors. [Copyright &y& Elsevier]
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- 2010
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12. Toxicity and genotoxicity evaluation of Passiflora alata Curtis (Passifloraceae)
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Boeira, Jane M., Fenner, Raquel, Betti, Andresa H., Provensi, Gustavo, Lacerda, Luciana de A., Barbosa, Patrícia R., González, Félix H.D., Corrêa, André M.R., Driemeier, David, Dall’Alba, Marília P., Pedroso, Annelise P., Gosmann, Grace, da Silva, Juliana, and Rates, Stela M.K.
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PASSIFLORA , *TOXICITY testing , *GENETIC toxicology , *PHARMACOPOEIAS - Abstract
Passiflora alata is an official species of Brazilian Pharmacopoeia and its aerial parts are used as medicinal plant by local population as well as constitutes many phytomedicines commercialized in Brazil as sedative. Aims of study: To evaluate the acute and sub-acute toxicity and genotoxicity of an aqueous spray-dried extract (PA) of Passiflora alata (2.6% flavonoids). Materials and methods: The acute and the sub-acute toxicity was evaluated in mice and rats, respectively. Behavioural, biochemical, hematological, histological and urine parameters were considered. Genotoxicity was assessed by using micronucleus test performed in peripheral blood and bone marrow cells and comet assay in peripheral blood leukocytes. Results: Mice deaths were not observed up to 4800mg/kg, p.o., single dose. Rats treated with aqueous extract at dose of 300mg/kg, p.o., for 14 days did not present biochemical, hematological or histopathological significant alterations when compared to control group. However, these rats showed signs of irritability and did not show weight gain. In addition, mice acutely treated with extract 150, 300 and 600mg/kg, p.o., presented DNA damage determined by comet assay in peripheral blood cells 3h after treatment. The effect of lower doses (12.5, 25 and 50mg/kg, p.o.) was evaluated at 3, 6 and 24h after treating. Only PA 50mg/kg (p.o.) induced significant damage at 3 and 6h. The maximum damage induction was observed at 6h. When the animals received PA 12.5, 25 or 50mg/kg/day during 3 days (i.e., 72h treatment) DNA damage (comet and micronucleus tests) increased significantly in a dose-dependent manner. Conclusion: In conclusion Passiflora alata presented genotoxic effect and deserves further toxicity evaluation in order to guarantee its safety for human use. [Copyright &y& Elsevier]
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- 2010
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13. Searching for multi-target antipsychotics: Discovery of orally active heterocyclic N-phenylpiperazine ligands of D2-like and 5-HT1A receptors
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Neves, Gilda, Menegatti, Ricardo, Antonio, Camila B., Grazziottin, Luiza R., Vieira, Renan O., Rates, Stela M.K., Noël, François, Barreiro, Eliezer J., and Fraga, Carlos A.M.
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TARGETED drug delivery , *ANTIPSYCHOTIC agents , *DRUG development , *HETEROCYCLIC compounds , *LIGANDS (Biochemistry) , *DRUG design , *SCHIZOPHRENIA treatment , *SEROTONIN - Abstract
Abstract: We described herein the design, synthesis, and pharmacological evaluation of N-phenylpiperazine heterocyclic derivatives as multi-target compounds potentially useful for the treatment of schizophrenia. The isosteric replacement of the heterocyclic ring at the biaryl motif generating pyrazole, 1,2,3-triazole, and 2-methylimidazole[1,2-a]pyridine derivatives resulted in 21 analogues with different substitutions at the para-biaryl and para-phenylpiperazine positions. Among the compounds prepared, 4 (LASSBio-579) and 10 (LASSBio-664) exhibited an adequate binding profile and a potential for schizophrenia positive symptoms treatment without cataleptogenic effects. Structural features of this molecular scaffold are discussed regarding binding affinity and selectivity for D2-like, 5-HT1A, and 5-HT2A receptors. [Copyright &y& Elsevier]
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- 2010
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14. Serotonergic neurotransmission mediates hypothermia induced by the N-phenylpiperazine antipsychotic prototypes LASSBio-579 and LASSBio-581
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Neves, Gilda, Kliemann, Michele, Betti, Andresa H., Conrado, Daniela J., Tasso, Leandro, Fraga, Carlos A.M., Barreiro, Eliezer J., Teresa Dalla Costa, and Rates, Stela M.K.
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NEUROTRANSMITTERS , *SCHIZOPHRENIA , *NEURAL transmission , *ANTIPSYCHOTIC agents - Abstract
Abstract: Previous studies have demonstrated that LASSBio-579 and LASSBio-581, two N-phenylpiperazine derivatives designed for the treatment of schizophrenia, are presynaptic dopamine D2 receptor agonists that induce a hypothermic effect in mice that is not mediated by dopamine receptor activation. The aim of the present study was to investigate possible serotonergic mechanisms underlying hypothermia induced by LASSBio-579 and LASSBio-581 in CF1 mice. The reduction in core temperature was dose-dependent (15–60 mg/kg, i.p.) and occurred by the oral route (30 mg/kg). Pretreatment with haloperidol (4 mg/kg, i.p.) resulted in a synergistic hypothermic effect. Pretreatment with (±)DOI (0.25 mg/kg, i.p.), a serotonin 5-HT2A/C receptor agonist, reduced the hypothermic effect induced by LASSBio-579 and LASSBio-581 at 15 and 30 mg/kg, i.p. In contrast, (±)DOI enhanced the hypothermia induced by both compounds at 60 mg/kg, i.p. The serotonin 5-HT1A antagonist WAY 100635 (0.05 mg/kg, s.c.) abolished the hypothermia induced by LASSBio-579 and diminished the hypothermia induced by LASSBio-581. Pretreatment with LASSBio579 (30 and 60 mg/kg, i.p.) and LASSBio-581 (60 mg/kg, i.p.) reduced the number of head-twitches induced by (±)DOI (2.5 mg/kg, i.p.). The ear-scratch response induced by (±)DOI was inhibited by both LASSBio-579 and LASSBio-581 at 60 mg/kg, i.p. These results indicate that LASSBio-579 and LASSBio-581 have mechanisms of action through the serotonergic neurotransmitter system. [Copyright &y& Elsevier]
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- 2008
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15. Comparisons between anxiety tests for selection of anxious and non anxious mice
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do-Rego, Jean-Claude, Viana, Alice F., Le Maître, Erwan, Deniel, Audrey, Rates, Stela M.K., Leroux-Nicollet, Isabelle, and Costentin, Jean
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PSYCHOLOGICAL stress , *BENZODIAZEPINES , *LABORATORY mice , *WORRY - Abstract
Abstract: Male Swiss albinos mice were submitted to two behavioural tests intended to determine their anxiety level: the elevated plus-maze test as well as the black and white compartments test. In addition they were submitted to the hole-board test. It was observed: (i) that the correlation between scores in the two first tests was weak, suggesting that they explore different components of anxiety; (ii) that the score on the latter test was better correlated with the response in the elevated plus-maze test than in the black and white compartments test. From these data three groups of animals were constituted, considered, respectively, as anxious, non anxious and intermediates. It was observed that both horizontal and vertical locomotion in an unfamiliar environment differed between groups, with higher activity in non anxious than in anxious. In the hole-board test, only animals classified as anxious displayed an obvious response to the anxiolytic drug diazepam (0.5mg/kg). Finally in the forced-swimming test, the three groups demonstrated a similar immobility time, suggesting that the operated segregation was not depending on a helpless component. It is proposed that the selection of mice from a combination of either elevated plus-maze and black and white compartments tests or a combination of hole-board test and black and white compartments test, allows to distinguish high or low anxiety animals among a population of mice. [Copyright &y& Elsevier]
- Published
- 2006
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16. Intermittent repeated stress but not ketamine changes mice response to antidepressants.
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Borsoi, Milene, Nunes, Luis Eduardo D., Barbosa, Amanda R., Lima, Mariana S., Medeiros, Isabelle, Pranke, Mariana A., Antonio, Camila B., Rates, Stela M.K., and Neves, Gilda A.
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KETAMINE , *MENTAL depression , *ANTIDEPRESSANTS , *MICE , *FLUOXETINE - Abstract
• Repeated ketamine anti-immobility effect lasted for 3 days after treatment. • Repeated intermittent stress impaired fluoxetine and imipramine anti-immobility effects. • Ketamine does not prevent stress-induced change in antidepressants' effect. Discovery of the rapid antidepressant effect of ketamine has been considered one of the most important advances in major depressive disorder treatment. Several studies report a significant benefit to patients that lasts up to 19 days after treatment. However, concerns arise from the long-term use of ketamine, thus a safe and effective strategy for maintaining its antidepressant effect is still necessary. To this end, our work assessed the effects of imipramine and fluoxetine after repeated ketamine treatment in male mice. Ketamine (30 mg/kg/day for 14 days) induced an anti-immobility effect in the forced swimming (FS) paradigm, detected 1 and 3 days after treatment. Seven days after the last ketamine injection, mice received imipramine (20 mg/kg) or fluoxetine (30 mg/kg). Imipramine and fluoxetine did not change mice's immobility time, regardless of the pre-treatment (saline or ketamine). Since both drugs' anti-immobility effect was demonstrated in the classical FS test, we can assume that repeated exposure to intermittent stress inhibited the antidepressant drugs' anti-immobility effects. Moreover, pre-exposure to ketamine did not counteract stress-induced changes in mice response to antidepressants. Since exposure to forced swim and i.p. injections are stressful to rodents, each stressor's contribution to the blunted response to antidepressants was investigated. Our data demonstrated that both stressors (FS and i.p. injections) influenced the reported effect. In summary, our results showed that exposure to intermittent repeated stress inhibited the anti-immobility effect of imipramine and fluoxetine in mice and corroborated findings demonstrating that exposure to stress can blunt patients' response to antidepressants. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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