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 KCI (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.
|Number of pages||5|
|Publication status||Published - 01-04-2005|
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