Cardioprotective and β-adrenoceptor antagonistic activity of a newly synthesized aryloxypropanolamine derivative PP-36

Abstract

Lokesh K Bhatt,1 Jyotika Bansal,2 Poonam Piplani,2 SL Bodhankar,3 A Veeranjaneyulu11Department of Pharmacology, School of Pharmacy and Technology Management, NMIMS University, Mumbai, India; 2University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India; 3Department of Pharmacology, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Erandawane, Pune, IndiaAbstract: The present study was performed to evaluate the cardioprotective effects and pharmacological characterization of newly synthesized β-adrenoreceptor antagonists 3-(3-tertbutylamino- 2-hydroxypropoxy)-4-methoxybenzaldehyde (PP-36) in the rat model of coronary artery occlusion and reperfusion. Pre-ischemic administration (20 minutes before coronary occlusion) of PP-36 showed cardioprotective effects against ischemia/reperfusion injury in rats. PP-36 (6 mg kg-1) significantly reduced arrhythmia score (6.33 ± 0.55, P < 0.05), infarct size/left ventricle size (38.9 ± 3.2, P < 0.05) and no mortality compared to vehicle-treated control group (14.17 ± 1.83, 44.9 ± 4.6 and 17% respectively). In-vitro studies in rat isolated right atria, guinea-pig trachea and rat distal colon preparations, were carried out to investigate the potency of PP-36 towards different β-adrenoceptor subtypes. pA2/pKB values of PP-36 for β1- β2- and β3-adrenoceptors were 6.904 ± 0.190, 6.44 ± 0.129 and 5.773 ± 0.129, respectively. In conclusion, PP-36 is a β-adrenoceptor antagonist possessing potent anti-arrhythmic and cardioprotective effects against ischemia/reperfusion injury in rats.Keywords: β-adrenoreceptors blocker, ischemia/reperfusion injury, arrhythmias, infarct area