Study of β-Adrenoreceptor Antagonistic Activity of DPJ 904 in Rats

Abstract

β-Adrenoreceptor antagonistic activity of a newly synthesized compound was evaluated in vivo by measuring the mean arterial blood pressure and heart rate of urethane-anesthetized rats treated with isoprenaline. In vitro β₁-, β₂- and β₃-antagonism was studied using isolated rat right atria, isolated rat uterus and isolated rat colon preparations, respectively, in comparison to isoprenaline response. DPJ 904 (1, 3 and 10 mg/kg, i.v.) produced dose-dependent hypotensive and bradycardia response in anesthetized rat. DPJ 904 (1, 3 and 10 mg/kg, i.v.) significantly inhibited both the tachycardial effects and hypotensive response induced by isoprenaline. DPJ 904-antagonized isoprenaline induced positive chronotropic effects of isolated rat right atria and a uterine relaxant effect indicating β₁- and β₂-blockade. The parallel shift to the right of the concentration-response curve of isoprenaline in the presence of DPJ 904 in KCl (30 mmol/l) induced contraction of the rat colon suggesting that DPJ 904 also possessed β₃-adrenoreceptor antagonistic activity. The selectivity to β₁-adrenoreceptor was nearly 20.5 times greater than to β₂-adrenoreceptor. The present study indicates that DPJ 904 possesses β-adrenoreceptor antagonistic activity with slightly more affinity to the β₁-adrenoreceptor subtype.