Pharmacological evaluation of ng5 and ng5* newly synthesized derivates of heteroarylamino-ethanols

Abstract

Heteroarylamino-ethanol’s derivatives can influence functions of the cardiovascular system. To obtain effective compounds able to favorably to influence those functions, a new series of are synthesized. Two of those compounds, which differ in the substitution on the heterocyclic benzofurane, were chosen for a basic pharmacological analysis. On the right atria of a guinea pig heart connected to an isometric transducer in Tyrode solution, we have evaluated the antagonist potency of the compounds; On Tracheal strip isolated and placed under a resting tension of 2 g in a bath filled with Krebs-Henseleit solution we evaluated the ability to antagonize relaxant effect and on isolated depolarized aorta adult Wister rats mounted in an organ bath filled with Krebs-Henseleit solution at 37°C and aerated with a pneumoxide under a resting tension of 1g we evaluated the inhibitory effect on the potassium-induced contraction at concentration 10-8 to 10-5 mol.l-1. Experiments on isolated beating guinea-pig atria both compounds at concentration: 1.0 × 10-6 mol.l-1 decreased basic heart rate and inhibited positive chronotropic effect of isoprenaline (pA2 = 6.70 ± 0.29 and/or 6.72 ± 0.23, resp.), and slightly influenced Isoprenaline-mediated relaxation of tracheal guinea pig muscle and relaxed KCl precontracted aortal strips of rats. The obtained results were compared with experiments on cardiovascular effect of hybrid heterorylamino-ethnols on intact animals. Both compounds given intraperitoneally at doses 5 and 25 mg/kg to the normotensive rats decreased mean arterial blood pressure in range of 7.7 –11.80 %. Both evaluated compounds could be regarded as candidates for further pharmacological and pharmacokinetic studies.