title: Novel tricyclic[2,1-f]theophylline derivatives of LCAP with activity in mouse models of affective disorders.
abstract: OBJECTIVE
  The purpose of this study was to investigate the central activity of the two new imidazo[2,1-f]purine-2,4-dione derivatives behaved as presynaptic 5HT1A receptor agonists and postsynaptic 5HT1A , 5HT2A and D2 receptors antagonists. The compounds were examined using animal tests towards antipsychotic, antidepressant- and anxiolytic-like properties and then compared with effects evoked by an atypical antipsychotic drug ziprasidone.
  
  
  METHODS
  D-amphetamine-induced hyperactivity test was used to determine antipsychotic-like activity of compounds 7 and 9. The forced swim test (FST) and the four-plate test were conducted to investigate antidepressant- and antianxiety-like activity, respectively, of studied agents. The investigated compounds 7, 9 and ziprasidone were administered intraperitoneally 60 min before the tests. Diazepam and imipramine were used as standard anxiolytic and antidepressant drugs, respectively.
  
  
  RESULTS
  The obtained results demonstrate that new synthesized compound 9 evokes antipsychotic-like activity alike ziprasidone and, in contrary to the antipsychotic drug, shows antidepressant- and anxiolytic-like properties in behavioural tests in mice.
  
  
  CONCLUSIONS
  The present preclinical results indicate that one of the two investigated imidazo[2,1-f]purine-2,4-dione derivatives, compound 9, with methyl group at 7 position of imidazo[2,1-f]purine-2,4-dione fragment and the ortho-OCH3 substituent in the aryl moiety, acts as an antipsychotic drug with additional antidepressant and anxiolytic properties.
authors.affiliation: Department of Clinical Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Partyka
authors.forename: Jakub
authors.initials: J
authors.lastname: Jarosz
authors.forename: Anna
authors.initials: A
authors.lastname: Wasik
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jastrzębska-Więsek
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zagórska
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawłowski
authors.forename: Anna
authors.initials: A
authors.lastname: Wesołowska
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000737:chemistry*; D013550:Swimming; D013806:Theophylline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D013806:Theophylline; D003913:Dextroamphetamine
keywords: antidepressant-like activity; axiolytic-like activity; imidazo[2,1-f]theophylline; ziprasidone