The hypotensive activity and alpha1-adrenoceptor antagonistic properties of some aroxyalkyl derivatives of 2-methoxyphenylpiperazine

摘要

In the search for new hypotesive agents a series of aroxyalkyl derivatives of 2-methoxyphenylpiperazine was obtained. The aim of the present study was to examine their hypotensive properties and to evaluate their mechanism of action. In the study their hypotensive activity after i.v. and p.o. administration, influence on the pressor responses to adrenaline, noradrenaline and methoxamine, direct spasmolytic and vasorelaxant effects were assessed. In the next step two compounds which were the most active and selective for α1- adrenoceptors were evaluated for their α1-adrenoreceptor subtypes selectivity in functional bioassays. The data from our experiments indicate that the hypotensive activity of tested aroxyalkyl derivatives of 2-methoxyphenylpiperazine is mainly a result of their α1- or α1/α2-adrenoceptor blocking properties. The two most active compounds showed to be the competitive antagonists of α1-adrenoceptors with stronger activity at α 1D-, α1A- and α1L- and weaker at α1B-subtype.