The possible mechanism of hypotensive activity of some pyrrolidin-2-one derivatives with antagonist properties at alpha1-adrenoceptors

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• 作者：Jacek Sapa ; ^{jaceksapa@interia.pl} ; Monika Kubacka
• 关键词：1-[3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl]-pyrrolidin-2-one derivative ; ¦Á-Adrenoceptor blocking activity ; Hypotensive activity
• 刊名：European Journal of Pharmacology
• 出版年：2011
• 出版时间：30 December, 2011
• 年：2011
• 卷：673
• 期：1-3
• 页码：40-48
• 全文大小：1K

文摘

In the search for new hypotensive agents a series of pyrrolidin-2-one derivatives was obtained with ¦Á-adrenoceptor blocking properties. The aim of the present study was to examine the possible involvement of other mechanisms in the observed hypotensive properties. In the present study the affinities for ¦Â₁-adrenoreceptors, vasorelaxant effect and the involvement in NO pathway of pyrrolidin-2-one derivatives were assessed. In the next step compounds were also evaluated for their ¦Á₁-adrenoreceptor subtypes in functional bioassays. The data from our experiments indicate that the hypotensive activity of tested pyrrolidin-2-one derivatives is a result of their ¦Á-adrenoceptor blocking properties and the compounds have stronger antagonist potency for the ¦Á_1D- than for ¦Á_1B-subtype. Among investigated compounds EP-46 is the most potent and selective antagonist for the ¦Á_1D- and ¦Á_1A- than for ¦Á_1B-subtype. Compound EP-43 can enhance NO production additionally.