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

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.