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.
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.
Department of Pharmacology, ICB, Federal University of Goiás, Goiânia, GO, Brazil.
Adriane F
AF
Brito
Department of Pharmacology, ICB, Federal University of Goiás, Goiânia, GO, Brazil.
James O
JO
Fajemiroye
Department of Pharmacology, ICB, Federal University of Goiás, Goiânia, GO, Brazil.
Hiasmin F S
HFS
Neri
Department of Pharmacology, ICB, Federal University of Goiás, Goiânia, GO, Brazil.
Dayane M
DM
Silva
Department of Pharmacology, ICB, Federal University of Goiás, Goiânia, GO, Brazil.
Daiany P B
DPB
Silva
Chemistry Institute, Laboratory of Chromatography and Mass Spectrometry, Federal University of Goiás, Goiânia, GO, Brazil.
Germán
G
Sanz
Chemistry Institute, Laboratory of Chromatography and Mass Spectrometry, Federal University of Goiás, Goiânia, GO, Brazil.
Boniek G
BG
Vaz
Chemistry Institute, Federal University of Goias, Goiânia, GO, Brazil.
Flávio S
FS
de Carvalho
Department of Pharmacology, ICB, Federal University of Goiás, Goiânia, GO, Brazil.
Paulo C
PC
Ghedini
Chemistry Institute, Federal University of Goias, Goiânia, GO, Brazil.
Luciano M
LM
Lião
Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goiás, Goiânia, GO, Brazil.
Ricardo
R
Menegatti
Department of Pharmacology, ICB, Federal University of Goiás, Goiânia, GO, Brazil.
Elson A
http://orcid.org/0000-0003-1996-0901
EA
Costa
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D010424:Pentobarbital / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects
C000623129:2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol; D014151:Anti-Anxiety Agents; D010879:Piperazines; D011720:Pyrazoles; D011978:Receptors, Nicotinic; D001569:Benzodiazepines; D010424:Pentobarbital
LQFM032; benzodiazepine site; nicotinic activity; piperazine derivative