β-Adrenoceptor antagonists are widely used in cardiovascular medicine. However, the main side effect of these drugs is due to antagonism of β2-adrenoceptors in the airways, resulting in bronchospasm. Therefore, more cardioselective β-blockers have been developed to offer a lower side effect profile. We have studied a new aryloxypropanolamine derivative (PP-34) with more cardioselectivity and efficacy against ischaemia/reperfusion injury in rats. Oxalate salts of 1-(tert-butylamino)-3-(5-tert-butylaminomethyl- 2-methoxyphenoxy) propan-2-ol (PP-34) is a novel β-adrenoceptor antagonist. 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-34 towards different β-adrenoceptor subtypes. pA2/pKB values of PP-34 for β1, β2, and β3 adrenoceptor were 7.89 ± 0.15, 6.13 ± 0.09 and 6.30 ± 0.19, respectively. The (β1/β2 selectivity ratio calculated was in the order of PP-34 > atenolol > propranolol. Pre-ischaemic administration (20 min before coronary occlusion) of PP-34 (0.3 or 1 mg kg-1) showed cardioprotective effects against ischaemia/reperfusion injury in rats and significantly reduced arrhythmias, infarct area and necrosis induced by ischaemia/reperfusion injury. The efficacy of PP-34 was found to be greater then atenolol. In conclusion, PP-34 is a cardioselective β-adrenoceptor antagonist, possessing potent anti-arrhythmic and cardioprotective effects against ischaemia/reperfusion injury in rats.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science