title: Involvement of the monoamine system in antidepressant-like properties of 4-(1-phenyl-1h-pyrazol-4-ylmethyl)-piperazine-1-carboxylic acid ethyl ester.
abstract: OBJECTIVE
  Piperazinic derivatives have therapeutic potential by acting as analgesic, antidepressant-like, anticonvulsant and antipsychotic in preclinical studies. In order to develop new drugs to treat mental disorders, we designed and synthesized the 4-(1-phenyl-1H-pyrazol-4-ylmethyl)-piperazine-1-carboxylic acid ethyl ester (PPMP), a new piperazine derivative with putative activities on central nervous system that seems to involve serotonergic system.
  
  
  METHODS
  In order to investigate the antidepressant-like activity of PPMP, mice were treated acutely and tested in the forced swimming test (FST) and tail suspension test. Pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., 4 days), and the non-selective blocker of catecholamine synthesis α-methyl para-tyrosine (AMPT, 100 mg/kg, i.p.) were used to assay the involvement of serotonergic and catecholaminergic systems. “Ex vivo” monoamine oxidase (MAO) enzymatic assay and quantification of hippocampal level of brain derived neurotrophic factor (BDNF) were carried out.
  
  
  RESULTS
  PPMP reduced the immobility time in both tests. PCPA or AMPT (100 mg/kg, i.p.) pretreatment blocked the effects of PPMP, thereby suggesting the involvement of serotonergic and catecholaminergic systems in the antidepressant-like effect of PPMP. PPMP did not inhibit the activity of MAO. Moreover, after 14 days of treatment, PPMP 15 mg/kg/day induced antidepressant-like effect and increased hippocampal level of BDNF. None of the treatments in this study altered the locomotor activity in the open field test.
  
  
  CONCLUSIONS
  In conclusion, PPMP demonstrates antidepressant-like effect that involve both serotonergic and catecholaminergic systems without inhibition of MAO activity. PPMP administration increased the hippocampal levels of BDNF.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil; Center of Biological Sciences and Health, Federal University of Western Bahia, Barreiras, BA, Brazil.
authors.forename: Pablinny Moreira
authors.initials: PM
authors.lastname: Galdino
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
authors.forename: Danillo Ramos
authors.initials: DR
authors.lastname: de Oliveira
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
authors.forename: Iziara Ferreira
authors.initials: IF
authors.lastname: Florentino
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
authors.forename: James Oluwagbamigbe
authors.initials: JO
authors.lastname: Fajemiroye
authors.affiliation: Laboratory of Cellular Pharmacology and Toxicology, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Marize Campos
authors.initials: MC
authors.lastname: Valadares
authors.affiliation: Laboratory of Cellular Pharmacology and Toxicology, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Soraia Santana
authors.initials: SS
authors.lastname: de Moura
authors.affiliation: Department of Physiological Sciences, Institute of Biology, Federal Rural University of Rio de Janeiro, Seropédica, RJ, Brazil.
authors.forename: Fábio Fagundes
authors.initials: FF
authors.lastname: da Rocha
authors.affiliation: Laboratory of Neuropharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Thereza Christina Monteiro
authors.initials: TC
authors.lastname: de Lima
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil. Electronic address: xico@ufg.br.
authors.forename: Elson Alves
authors.initials: EA
authors.lastname: Costa
authors.affiliation: Laboratory of Medicinal Pharmaceutical Chemistry, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Menegatti
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D041702:BALB 3T3 Cells; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism*; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D012701:Serotonin / Q000378:metabolism*; D013550:Swimming
chemical_list: C574301:4-(1-phenyl-1H-pyrazol-4-ylmethyl)piperazine-1-carboxylic acid ethyl ester; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D002395:Catecholamines; D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D011720:Pyrazoles; D012701:Serotonin
keywords: AMPT; Antidepressant-like effect; BDNF; MAO activity; PCPA