Selective β₁-adrenoreceptor blocking activity of newly synthesized acyl amino-substituted aryloxypropanolamine derivatives, DPJ 955 and DPJ 890, in rats.

Nandakumar, K.; Bansal, S. K.; Singh, Randhir; Bodhankar, S. L.; Jindal, D. P.; Coumar, Mohane S.; Balaraman, R.; Bhardwaj, S. H.

The in-vivo β-adrenoreceptor antagonistic activity of test compounds DPJ 955 and DPJ 890 was assessed against β-adrenoreceptor agonist (isoprenaline) induced tachycardia in anaesthetized rats. The selectivity to block isoprenaline responses on different β-adrenoreceptor subtypes (β1, β2 and β3) of the test compounds was carried out on isolated rat right atria, isolated rat uterus and isolated rat colon preparations, respectively. Intravenous injection of isoprenaline alone in anaesthetized rats caused hypotension and tachycardia. DPJ 955 or DPJ 890 alone produced a fall in mean arterial pressure and bradycardia in a dose-dependent manner. Administration of isoprenaline to anaesthetized rats pre-treated with test compounds significantly blocked both the tachycardial and hypotensive responses induced by isoprenaline. The test compounds shifted the concentration response curves of isoprenaline towards the right for isolated rat right atrial preparations, rat uterus and rat colon, indicating β1, β2 and β3 adrenoreceptor blockade, respectively. The selectivity ratio for β1/β-adrenoreceptors to DPJ 955 and DPJ 890 was 64.6 and 83.2, respectively. DPJ 890 was more potent in blocking β1-adrenoreceptors and was more selective towards β1 receptors than to other β-adrenoreceptor subtypes. In conclusion, DPJ 955 and DPJ890 have β-adrenoreceptor blocking activity with high selectivity for the β1-adrenoreceptor subtype.

Journal of Pharmacy & Pharmacology, 2005, Vol 57, Issue 4, p515

0022-3573

Academic Journal

10.1211/0022357055768