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.

Keywords: Piperazine derivatives; Selectivity; Xanthone derivatives; α(1)-Adrenoceptor subtype.