title: The anxiolytic-like activity of a novel N-cycloalkyl-N-benzoylpiperazine derivative.
abstract: BACKGROUND
  Anxiety-related disorders are among the most common mental illnesses in the world for which benzodiazepines, buspirone and antidepressant drugs remain the first-line treatment. These drugs have good efficacy but they have numerous disadvantages, such as drug abuse potential, delayed onset of action or tolerance. A literature review reveals that a variety of piperazine derivatives may exhibit interesting pharmacological properties, including anxiolytic-like, antidepressant, nootropic and antinociceptive activities demonstrated in animal models, as well as an antioxidant capacity shown in some in vitro tests. Hence, the aim of this study was the synthesis and preliminary pharmacological in vivo evaluation of a novel N-cycloalkyl-N-benzoylpiperazine derivative, compound 9.
  
  
  METHODS
  The test compound 9 was synthesized from a cyclic ketone 6,6-dimethylbicyclo[3.1.0]hexan-3-one (compound 7) and N-benzoylpiperazine. The final product was evaluated in vivo for its anxiolytic-like and antinociceptive activity after intraperitoneal (ip) administration. Its impact on animals' locomotor activity and motor performance was also evaluated.
  
  
  RESULTS
  At the dose of 50mg/kg the test compound 9 showed statistically significant (p<0.01) anxiolytic-like activity in the four plate test. This effect was completely abolished by pretreatment with naloxone hydrochloride (1mg/kg; ip). Compound 9 did not influence animals' locomotor activity or motor coordination. No antinociceptive effect was demonstrated in the hot plate test.
  
  
  CONCLUSIONS
  The anxiolytic-like properties of N-bicyclo-[3.1.0]hexyl derivative (9) in the four plate test are mediated by the opioid system. The results obtained make this compound a promising lead structure for further development of anxiolytic drugs.
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wrocław, Poland.
authors.forename: Daniel Jan
authors.initials: DJ
authors.lastname: Strub
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University, Kraków, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Sałat
authors.affiliation: Department of Radioligands, Faculty of Pharmacy, Jagiellonian University, Kraków, Poland. Electronic address: mflibrow@cyf-kr.edu.pl.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Librowski
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wrocław, Poland; Institute of Cosmetology, Wrocław College of Physiotherapy, Wrocław, Poland.
authors.forename: Stanisław
authors.initials: S
authors.lastname: Lochyński
authors.affiliation: Department of Radioligands, Faculty of Pharmacy, Jagiellonian University, Kraków, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gaweł
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University, Kraków, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Podkowa
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects / Q000523:psychology; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014151:Anti-Anxiety Agents; D010879:Piperazines; D009270:Naloxone
keywords: Antinociceptive activity; Anxiolytic-like activity; N-benzoylpiperazine derivatives; Naloxone hydrochloride; Reductive amination