Study of Beta-adre Oreceptor Blocki G a D a Tihyperte Sive Activity of a Ewly Sy Thesized Aryloxypropa Olami E Derivative, Pp-28 I Laboratory a Imals

Beta-adrenoceptor blockers are an important class of drugs used in management of patient with cardiovascular diseases. These drugs have been shown to reduced mortility in hypertension. However, the main side effect of these drugs is due to antagonism of β2adrenoceptors in the airways, resulting in bronchospasm. Therefore, more cardio selective betablockers have been developed to offer a lower side effect profile. We have studied a new aryloxypropanolamine derivative (PP-28) with more cardio selectivity and efficacy against hypertension in rats. Oxalate salts of 1-tert-butylamino-3-[3-(tert-butylamino-methyl)-phenoxy]propan-2-ol. (PP-28) is a novel beta-adrenoceptor antagonist. In-vitro studies in rat isolated right atria, rat uterus and rat distal colon preparations were carried out to investigate the potency of PP-28 towards different beta-adrenoceptor subtypes. The pA2 values of PP-28 for β1, β2, and β3 adrenoceptor were 7.69+/-0.10, 6.03+/-0.08 and 6.10+/-0.14, respectively. The β1/ β2 selectivity ratio calculated was in the order of PP-28 > atenolol > propranolol. PP-28 also blocked significantly isoprenaline induced tachycardia and hypotensive responses in anesthetized rat.Antihypertensive effect of PP-28 was observed in left renal artery ligated (LRA) and 10% Fructose induce hypertensive rat.Treatment with PP-28 (1, 3 and 10 mg/kg, orally) produced a dose dependent decrease in MAP and heart rate of LRA ligated rats as well as 10% Fructose induce hypertensive rat .The efficacy of PP-28 was found to be greater then atenolol. In conclusion, PP-28 is a cardioselective beta-adrenoceptor antagonist, possessing potent Antihypertensive effects in left renal artery ligated and 10% Fructose induce hypertensive rat