Department of Pharmacodynamic, Laboratory of Pharmacological Screening, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.
Eur J Pharmacol. 2011 Dec 30;673(1-3):40-8. doi: 10.1016/j.ejphar.2011.05.010. Epub 2011 May 18.
In the search for new hypotensive agents a series of pyrrolidin-2-one derivatives was obtained with α-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 β₁-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 α₁-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 α-adrenoceptor blocking properties and the compounds have stronger antagonist potency for the α(1D)- than for α(1B)-subtype. Among investigated compounds EP-46 is the most potent and selective antagonist for the α(1D)- and α(1A)- than for α(1B)-subtype. Compound EP-43 can enhance NO production additionally.
在寻找新的降压剂的过程中，得到了一系列具有α-肾上腺素能受体阻断特性的吡咯烷-2-酮衍生物。本研究的目的是研究在观察到的降压特性中可能涉及的其他机制。在本研究中，评估了吡咯烷-2-酮衍生物对β₁-肾上腺素能受体的亲和力、血管舒张作用以及对 NO 途径的参与。在下一步中，还对化合物在功能性生物测定中对 α₁-肾上腺素能受体亚型的作用进行了评估。我们的实验数据表明，所测试的吡咯烷-2-酮衍生物的降压活性是其 α-肾上腺素能受体阻断特性的结果，并且这些化合物对 α(1D)-亚型的拮抗作用比 α(1B)-亚型更强。在研究的化合物中，EP-46 对 α(1D)-和 α(1A)-亚型的拮抗作用比 α(1B)-亚型更强，选择性也更高。化合物 EP-43 还可以额外增强 NO 的产生。
