Ecarazine Hydrochloride, Hydralazineおよび代謝物のPhosphodiesterase阻害活性について

概要

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The inhibitory effects of ecarazine hydrochloride, hydralazine and some of their metabolites were compared on purified beef heart phosphodiesterase activity and bariumelicited smooth muscle contraction. 1) Ecarazine hydrochloride and hydralazine exhibited weak inhibition on cyclic AMP phosphodiesterase (PDE). The IC_<50> values (concentration of inhibition resulting in 50 per cent of inhibition) were 2.4×10^<-3>M for ecarazine hydrochloride and >5×10^<-3>M for hydralazine. On the other hand, the metabolites, s-triazolo [3,4-a] phthalazine-2H-3-one (IC_<50> 8.3×10^<-5>M) and 3-methyl-s-triazolo [3,4-a] phthalazine (IC_<50> 4.9×10^<-4>M) and the derivatives, 3-propyl-s-triazolo [3,4-a] phthalazine (IC_<50> 2.5×10^<-4>M) and 3-ethyl-s-triazolo-[3,4-a] phthalazine (IC_<50> 3.1×10^<-4>M) were potent PDE inhibitors and had the same grade of potency as theophylline. 2) The magnitude of the relaxant effect of s-triazolo [3,4-a] phthalazine derivatives on Ba^<2+> contracture was greater than that of ecarazine hydrochloride and hydralazine and this activity correlated with PDE inhibition. The other metabolites, 1-(2H)-phthalazinone, phthalazine and 3-hydroxymethyl-s-triazolo [3,4-a] phthalazine were the least potent. 3) No antihypertensive activity of these metabolites and derivatives on the blood pressure of spontaneously hypertensive rats was observed.
社団法人日本薬学会の論文
1979-05-25