PMID- 26569034
OWN - NLM
STAT- MEDLINE
DCOM- 20160408
LR  - 20151215
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 143
DP  - 2015 Dec 15
TI  - Involvement of the monoamine system in antidepressant-like properties of 
      4-(1-phenyl-1h-pyrazol-4-ylmethyl)-piperazine-1-carboxylic acid ethyl ester.
PG  - 187-93
LID - S0024-3205(15)30072-2 [pii]
LID - 10.1016/j.lfs.2015.11.009 [doi]
AB  - AIMS: 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. MATERIALS AND 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 
      alpha-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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
FAU - Galdino, Pablinny Moreira
AU  - Galdino PM
AD  - Department of Pharmacology, Institute of Biological Sciences, Federal University 
      of Goias, Campus Samambaia, Goiania, GO, Brazil; Center of Biological Sciences 
      and Health, Federal University of Western Bahia, Barreiras, BA, Brazil.
FAU - de Oliveira, Danillo Ramos
AU  - de Oliveira DR
AD  - Department of Pharmacology, Institute of Biological Sciences, Federal University 
      of Goias, Campus Samambaia, Goiania, GO, Brazil.
FAU - Florentino, Iziara Ferreira
AU  - Florentino IF
AD  - Department of Pharmacology, Institute of Biological Sciences, Federal University 
      of Goias, Campus Samambaia, Goiania, GO, Brazil.
FAU - Fajemiroye, James Oluwagbamigbe
AU  - Fajemiroye JO
AD  - Department of Pharmacology, Institute of Biological Sciences, Federal University 
      of Goias, Campus Samambaia, Goiania, GO, Brazil.
FAU - Valadares, Marize Campos
AU  - Valadares MC
AD  - Laboratory of Cellular Pharmacology and Toxicology, Faculty of Pharmacy, Federal 
      University of Goias, Goiania, GO, Brazil.
FAU - de Moura, Soraia Santana
AU  - de Moura SS
AD  - Laboratory of Cellular Pharmacology and Toxicology, Faculty of Pharmacy, Federal 
      University of Goias, Goiania, GO, Brazil.
FAU - da Rocha, Fabio Fagundes
AU  - da Rocha FF
AD  - Department of Physiological Sciences, Institute of Biology, Federal Rural 
      University of Rio de Janeiro, Seropedica, RJ, Brazil.
FAU - de Lima, Thereza Christina Monteiro
AU  - de Lima TC
AD  - Laboratory of Neuropharmacology, Federal University of Santa Catarina, 
      Florianopolis, SC, Brazil.
FAU - Costa, Elson Alves
AU  - Costa EA
AD  - Department of Pharmacology, Institute of Biological Sciences, Federal University 
      of Goias, Campus Samambaia, Goiania, GO, Brazil. Electronic address: xico@ufg.br.
FAU - Menegatti, Ricardo
AU  - Menegatti R
AD  - Laboratory of Medicinal Pharmaceutical Chemistry, Faculty of Pharmacy, Federal 
      University of Goias, Goiania, GO, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151110
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (4-(1-phenyl-1H-pyrazol-4-ylmethyl)piperazine-1-carboxylic acid ethyl ester)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Catecholamines)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Pyrazoles)
RN  - 333DO1RDJY (Serotonin)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology/*therapeutic use
MH  - BALB 3T3 Cells
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Catecholamines/*metabolism
MH  - Depression/*drug therapy/*metabolism
MH  - Hindlimb Suspension
MH  - Male
MH  - Mice
MH  - Monoamine Oxidase Inhibitors/pharmacology/therapeutic use
MH  - Piperazines/pharmacology/*therapeutic use
MH  - Pyrazoles/pharmacology/*therapeutic use
MH  - Serotonin/*metabolism
MH  - Swimming
OTO - NOTNLM
OT  - AMPT
OT  - Antidepressant-like effect
OT  - BDNF
OT  - MAO activity
OT  - PCPA
EDAT- 2015/11/17 06:00
MHDA- 2016/04/09 06:00
CRDT- 2015/11/17 06:00
PHST- 2015/06/26 00:00 [received]
PHST- 2015/11/05 00:00 [revised]
PHST- 2015/11/10 00:00 [accepted]
PHST- 2015/11/17 06:00 [entrez]
PHST- 2015/11/17 06:00 [pubmed]
PHST- 2016/04/09 06:00 [medline]
AID - S0024-3205(15)30072-2 [pii]
AID - 10.1016/j.lfs.2015.11.009 [doi]
PST - ppublish
SO  - Life Sci. 2015 Dec 15;143:187-93. doi: 10.1016/j.lfs.2015.11.009. Epub 2015 Nov 
      10.