ABSTRACT
beta-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 beta(1)-, beta(2)- and beta(3)-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 beta(1)- and beta(2)-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 beta(3)-adrenoreceptor antagonistic activity. The selectivity to beta(1)-adrenoreceptor was nearly 20.5 times greater than to beta(2)-adrenoreceptor. The present study indicates that DPJ 904 possesses beta-adrenoreceptor antagonistic activity with slightly more affinity to the beta(1)-adrenoreceptor subtype.
