The anxiolytic-like activity of a novel N-cycloalkyl-N-benzoylpiperazine derivative.
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.
['Strub|Daniel Jan|DJ|', 'Sałat|Kinga|K|', 'Librowski|Tadeusz|T|', 'Lochyński|Stanisław|S|', 'Gaweł|Magdalena|M|', 'Podkowa|Adrian|A|']
D000818:Animals D014151:Anti-Anxiety Agents D001007:Anxiety D004305:Dose-Response Relationship, Drug D008297:Male D051379:Mice D009043:Motor Activity D009270:Naloxone D010147:Pain Measurement D010879:Piperazines
Anxiolytic-like activity Antinociceptive activity Naloxone hydrochloride N-benzoylpiperazine derivatives Reductive amination