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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Different pharmacological characteristics of structurally similar benzylisoquinoline analogs, papaverine, higenamine, and GS 389, on isolated rat aorta and heart.

In the present study, we compared the pharmacological properties of structurally similar benzylisoquinoline compounds, papaverine, higenamine, and GS 389, using isolated rat aorta and atrial preparations. The three benzylisoquinoline compounds, concentration dependently, relaxed phenylephrine (3 microM) induced contraction of rat aortic rings, with the rank order of potency being higenamine > papaverine > GS 389. They also relaxed high K+ (60 mM) induced contraction, with the rank order of potency being papaverine > GS 389 >> higenamine. The relaxation was not modified by the presence of endothelium. To assess whether these compounds directly interfere with Ca2+ influx, the effects of these compounds on Ca(2+)-induced contraction in Ca(2+)-free media were examined. Among the three compounds, papaverine most strongly inhibited Ca(2+)-induced contraction of both K+ stimulated and phenylephrine-stimulated aorta. Higenamine was least potent in inhibition of Ca(2+)-induced contraction in high K+ depolarized aorta. In atrial tissues, lower concentrations of papaverine increased spontaneous beats and isometric tension, whereas above 30 microM its action was reversed. GS 389 decreased heart rate without affecting the contractility. On the other hand, higenamine concentration dependently increased both heart rate and isometric tension, as well as cyclic AMP levels in atrial tissues as a result of beta-receptor activation. Cyclic AMP and cyclic GMP dependent phosphodiesterases from rat atrial and ventricular tissue homogenates were inhibited by papaverine and GS 389, but not by higenamine. These results suggest that calcium antagonistic action of these compounds is at least in part responsible for vasodilation action, but not for cardiac action.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

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