Antiarrhythmic, hypotensive and alpha(1)-adrenolytic properties of new 2-methoxyphenylpiperazine derivatives of xanthone

作者：Rapacz Anna^*; Pytka Karolina; Sapa Jacek; Kubacka Monika; Filipek Barbara; Szkaradek Natalia; Marona Henryk

来源：European Journal of Pharmacology, 2014, 735: 10-16.

DOI：10.1016/j.ejphar.2014.04.010

• Antiarrhythmic
• Hypotensive
• alpha(1)-adrenoceptor antagonist
• Xanthone derivatives
• Piperazine derivatives

The main goal of this study was to assess antiarrhythmic and hypotensive activity of new 2-methoxyphenylpiperazine derivatives of xanthone. In order to better understand mechanism of action of studied compounds, their abilities to antagonize the increase in blood pressure elicited by adrenaline, noradrenaline and methoxamine, as well as the antagonistic properties for alpha(1)-adrenoceptors on isolated rat aorta were evaluated. Therapeutic antiarrhythmic activity was investigated in an adrenaline-induced model of arrhythmia. Hypotensive activity in normotensive rats was evaluated after oral administration. Influence on blood vasopressor response and alpha(1)-adrenoceptors in rat thoracic aorta was evaluated to determine if the observed cardiovascular effects could be related to alpha(1)-adrenolytic properties. Tested compounds produced antiarrhythmic and hypotensive activity. The most active compound was MH-99 - (R,S)-4-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride. All studied compounds showed alpha(1)-adrenolytic properties in the in vivo and in vitro tests. The results indicate that the new valuable compounds with antiarrhythmic and hypotensive activity might be found in the group of xanthone derivatives. Further pharmacological utility of these compounds should be investigated.

• 出版日期2014-7-15