title: 7-3-Chlorophenypiperazinylalkyl derivatives of 8-alkoxy-purine-2,6-dione as a serotonin receptor ligands with potential antidepressant activity.
abstract: BACKGROUND
  The previous study showed that arylpiperazine can condition affinity to α-adrenoceptors, 5-HT1A/5-HT2A receptors and compounds with arylpiperazine had antidepressant-like effect. The aim of this study was to determine the antidepressant-like activity of new arylpiperazines containing novel 8-alkoxy-purine-2,6-dione fragments.
  
  
  METHODS
  New 3-chloroarylpiperazinylalkyl analogs of 8-alkoxy-purine-2,6-dione and their purine-2,6,8-trione analogs (2-5) were tested for their α1, α2, 5-HT1A,5-HT2A, and 5-HT7 receptor affinities in radioreceptor binding study. Moreover, in search for potential antidepressant properties of these compounds, the forced swim test in mice was conducted.
  
  
  RESULTS
  Compounds 2 and 3 were potent 5-HT1A receptor ligands with Ki within the range on 12-15 nM. All investigated compounds were found to be highly active 5-HT2A receptor (Ki 15-28 nM) and α1 adrenoceptor (Ki 21-89 nM) ligands. In the forced swim test all the compounds showed a significantly activity in spite of their reducing ability of locomotor activity. The most potent effect was produced by compound 4 and 5, which reduced the immobility time in this test in all used doses.
  
  
  CONCLUSIONS
  In our study the most potent antidepressant-like activity was produced by compounds 4 and 5, which are selective for the 5-HT2A and α1 receptors.
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland. Electronic address: gogol67@interia.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.affiliation: Chair of Pharmaceutical Chemistry, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Chłoń-Rzepa
authors.affiliation: Chair of Pharmaceutical Chemistry, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zagórska
authors.affiliation: Chair of Pharmacobiology, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.affiliation: Chair of Pharmaceutical Chemistry, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawłowski
authors.affiliation: Chair of Pharmacobiology, Jagiellonian University, Medical College, Kraków, Poland; Laboratory of Trace Elements Neurobiology, Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences and Center of Excellence in Neuropsychopharmacology, Kraków, Poland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D008024:Ligands; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013550:Swimming / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D008024:Ligands; D010879:Piperazines; D011687:Purines; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C030985:purine
keywords: Adrenergic; Forced swim test; Purine-2,6-diones; Receptors; Serotonergic