β-Blocking activity of PP-34, a newly synthesized aryloxypropanolamine derivative, and its cardioprotective effect against ischaemia/reperfusion injury in laboratory animals

Lokesh K. Bhatt, K. Nandakumar, S. L. Bodhankar, Jyotika Bansal, Poonam Piplani

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 (β12 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.

Original languageEnglish
Pages (from-to)429-436
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume59
Issue number3
DOIs
Publication statusPublished - 01-03-2007

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Laboratory Animals
Reperfusion Injury
Adrenergic Receptors
Atenolol
Bronchial Spasm
Oxalates
Coronary Occlusion
Anti-Arrhythmia Agents
Trachea
Heart Atria
Drug-Related Side Effects and Adverse Reactions
Propranolol
Cardiac Arrhythmias
Guinea Pigs
Colon
Necrosis
Salts
Medicine

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

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title = "β-Blocking activity of PP-34, a newly synthesized aryloxypropanolamine derivative, and its cardioprotective effect against ischaemia/reperfusion injury in laboratory animals",
abstract = "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.",
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β-Blocking activity of PP-34, a newly synthesized aryloxypropanolamine derivative, and its cardioprotective effect against ischaemia/reperfusion injury in laboratory animals. / Bhatt, Lokesh K.; Nandakumar, K.; Bodhankar, S. L.; Bansal, Jyotika; Piplani, Poonam.

In: Journal of Pharmacy and Pharmacology, Vol. 59, No. 3, 01.03.2007, p. 429-436.

Research output: Contribution to journalArticle

TY - JOUR

T1 - β-Blocking activity of PP-34, a newly synthesized aryloxypropanolamine derivative, and its cardioprotective effect against ischaemia/reperfusion injury in laboratory animals

AU - Bhatt, Lokesh K.

AU - Nandakumar, K.

AU - Bodhankar, S. L.

AU - Bansal, Jyotika

AU - Piplani, Poonam

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N2 - 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.

AB - 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.

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