Open Accessβ‐adrenoreceptor blocking and antihypertensive activity of PP‐24, a newly synthesized aryloxypropanolamine derivative
Author(s) -
Nikam Aniket P.,
Bodhankar Subhash L.,
Piplani Poonam,
Bansal Jyotika,
Thakurdesai Prasad A.
Publication year - 2008
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/jpp.60.11.0011
Subject(s) - atenolol , propranolol , isoprenaline , potency , endocrinology , blood pressure , medicine , bradycardia , antagonist , tachycardia , prazosin , pharmacology , chemistry , heart rate , receptor , in vitro , biochemistry , stimulation
PP‐24 is a newly synthesized putative β‐adrenoceptor antagonist. The objective of the study was to the evaluate β‐adrenoceptor blocking activity of PP‐24 on isolated rat preparations: right atria, uterus and colon. Effects on the rat ECG and renal hypertension (induced by left renal artery ligation) were also investigated. Treatment with PP‐24 (3 and 10 mg kg −1 ) for 7 days in rats with renal hypertension significantly reduced the mean atrial blood pressure. Single i.v. injections of isoprenaline (0.3, 1 and 3 μg kg −1 ) alone in normal anaesthetized rat caused hypotension and tachycardia, while PP‐24 alone produced dose‐dependent falls in mean aterial pressure and bradycardia. Pretreatment of anaesthetized rats with test compounds significantly blocked the hypotension response but not the tachycardia induced by isoprenaline (0.3, 1 and 3 μg kg −1 ). The pA 2 of PP‐24 to β 1 ‐, β 2 ‐ and β 3 ‐adrenoceptors was 7.72 ± 0.082, 7.40 ± 0.082 and 6.39 ± 0.16, respectively. The β 1 /β 2 selectivity ratio was 2.08, compared with 1.27 for propranolol and 39.17 for atenolol. It is concluded that PP‐24 possesses β‐adrenoceptor blockade activity but with non‐specific affinity for β 1 ‐ and β 2 ‐adrenoceptor subtypes. The rank order of potency of the antagonists for β 1 ‐adrenoceptors was atenolol > PP‐24 > propranolol. The antihypertensive activity of PP‐24 in rats with renal hypertension appears to be due to blockade of β‐adrenoceptors.