title: The hypotensive activity and alpha1-adrenoceptor antagonistic properties of some aroxyalkyl derivatives of 2-methoxyphenylpiperazine.
abstract: 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 α(1)-adrenoceptors were evaluated for their α(1)-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 α(1)- or α(1)/α(2)-adrenoceptor blocking properties. The two most active compounds showed to be the competitive antagonists of α(1)-adrenoceptors with stronger activity at α(1D)-, α(1A)- and α(1L)- and weaker at α(1B)-subtype.
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland. mfkuback@cyf-kr.edu.pl
authors.forename: Monika
authors.initials: M
authors.lastname: Kubacka
authors.forename: Szczepan
authors.initials: S
authors.lastname: Mogilski
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.forename: Henryk
authors.initials: H
authors.lastname: Marona
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D055808:Drug Discovery; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D011189:Potassium Chloride