Beta-blocking activity of PP-34, a newly synthesized aryloxypropanolamine derivative, and its cardioprotective effect against ischaemia/reperfusion injury in laboratory animals.
Beta-adrenoceptor antagonists are widely used in cardiovascular medicine. However, the main side effect of these drugs is due to antagonism of beta(2)-adrenoceptors in the airways, resulting in bronchospasm. Therefore, more cardioselective beta-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 beta-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 beta-adrenoceptor subtypes. pA(2)/pK(B) values of PP-34 for beta(1), beta(2), and beta(3) adrenoceptor were 7.89+/-0.15, 6.13+/-0.09 and 6.30+/-0.19, respectively. The beta(1)/beta(2) 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 beta-adrenoceptor antagonist, possessing potent anti-arrhythmic and cardioprotective effects against ischaemia/reperfusion injury in rats.
Bhatt
Lokesh K
LK
Department of Pharmacology, Poona College of Pharmacy, Bharti Vidyapeeth Deemed University, Erandwane, Pune 411038, India.
Nandakumar
K
K
Bodhankar
S L
SL
Bansal
Jyotika
J
Piplani
Poonam
P
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D001262:Atenolol / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D009336:Necrosis; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*
C519077:1-(tert-butylamino)-3-(5-tert-butylaminomethyl-2-methoxyphenoxy)propan-2-ol; D000319:Adrenergic beta-Antagonists; D001596:Benzylamines; D011412:Propanolamines; D001262:Atenolol; D011433:Propranolol