title: Biofunctional studies of new 2-methoxyphenylpiperazine xanthone derivatives with α₁-adrenolytic properties.
abstract: BACKGROUND
  The aim of this study was to assess the selectivity of the studied xanthone derivatives for α1-adrenoceptor subtypes (α1A, α1B, α1D, α1L) in functional experiments in order to verify if they possess any selectivity for a distinct subtype of α1-adrenoceptor. Moreover, several pharmacological tests were carried out to assess whether they reveal other than α1-adrenoceptor blocking properties such as: antagonistic for 5-HT2 receptors, vasorelaxant or spasmolytic.
  
  
  METHODS
  The influence on α1A-adrenoceptors was examined in biofunctional studies employing isolated rat vas deferens, on α1B-adrenoceptors in guinea-pig spleen, on α1D-adrenoceptors in rat aorta, and on α1L-adrenoceptors in rabbit spleen. Affinity for 5-HT2 receptors was measured in radioligand binding assay, whereas antagonistic potency for 5-HT2 receptors was studied on isolated rat aorta. Vasorelaxant effect of tested compounds was assessed in functional study employing rat aorta, whereas direct spasmolytic activity was investigated using the isolated rabbit small intestine.
  
  
  RESULTS
  The present study provides evidences that the tested 2-methoxyphenylpiperazine xanthone derivatives are non-selective α1-adrenoceptor blockers. However, at higher concentrations the direct spasmolytic effect could enhance their hypotensive activity. The obtained results indicate that the studied xanthones possessed weak calcium entry blocking activity, as well as antagonistic properties for 5-HT2A receptors.
  
  
  CONCLUSIONS
  The results of the present study support the idea that the hypotensive activity of the studied compounds is related to their α1-adrenolytic properties.
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland. Electronic address: a.rapacz@uj.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Rapacz
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: Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Nowiński
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Szczepan
authors.initials: S
authors.lastname: Mogilski
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Pytka
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.affiliation: Department of Cytobiology and Histochemistry, Laboratory of Pharmacobiology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Szkaradek
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Marona
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D013154:Spleen / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology*
chemical_list: C000610387:4-(2-acetoxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one; C000610386:4-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one; C000610385:4-(3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one; D058668:Adrenergic alpha-1 Receptor Antagonists; D015220:Calcium Channels; D010879:Piperazines; D044348:Receptors, Serotonin, 5-HT2; D044004:Xanthones; D011189:Potassium Chloride
keywords: Piperazine derivatives; Selectivity; Xanthone derivatives; α(1)-Adrenoceptor subtype