著者

榊原 仁作 永井 慎一 森 淳 竹谷 和視 堀田 芳弘

出版者

日本生薬学会

雑誌

生薬学雑誌 (ISSN:00374377)

巻号頁・発行日

vol.40, no.3, pp.p317-324, 1986-09

---

20R-Dihydroouabain (20R-DHO) and 20S-dihydroouabain (20S-DHO) were synthesized by reduction of ouabain (G-strophanthin) and separated by reversed phase high performance liquid chromatography. The relationships between the stereochemical structures and pharmacological activities of 20R- and 20S-DHO were studied by the use of isolated guinea-pig papillary muscle and renal Na^+, K^+-ATPase. 20S-DHO was more inotropic (pD_2: 5.0, 100% increase in contractile force at 3.0 x 10^<-5> M) and more inhibitory (pIC_<50>: 5.9) than 20R-DHO (pD_2: 4.6, 100% increase in contractile force at 1.0 × 1O^<-4> M, pIC_<50>: 5.5). On the other hand, both R and S compounds inhibited the positive inotropic effect of their parent compound ouabain; the potency of inhibition by 20S-DHO was greater than that by 20R-DHO. These results suggest that the pharmacological differences in 20R- and 20S-DHO may depend on the strength of hydrogen bond between the carbonyl oxygen and Na^+, K^+-ATPase receptor.