The structure-activity relationship of a novel natural substance murrayaquinone-A and related compounds, was studied by evaluating their positive inotropic potencies on guinea-pig papillary muscle in Krebs-Henseleit solution. Among the selected eight compounds, menadione and plumbagin (aromatic methyl-p-quinone) induced a potent triphasic inotropic response, as reported previously for murrayaquinone-A. The order of potency of these active compounds was: plumbagin (pD2 = 6.40) greater menadione (pD2 = 5.70) greater than murrayaquinone-A (pD2 = 5.27). Demethyl derivatives of aromatic methyl-p-quinones (carbazolequinone, 1,4-naphthoquinone and 2-hydroxy-1,4-naphthoquinone) and methyl-benzoquinones (co-enzyme Q10 and 2-methyl-1,4-benzoquinone) did not produce any positive inotropic effect. It is concluded that the presence of the aromatic methyl-p-quinone skeleton is essential for the development of an inotropic response. A common mechanism for this positive inotropic effect is suggested by the fact that in all cases it was triphasic in nature and inhibited in anoxic conditions or by 2,4-dinitrophenol and dicumarol.

Alkaloids↗

PubMedDate not supplied

Comparison of the cardiovascular effects of three dihydropyridine compounds.

Three dihydropyridine compounds with 2-carbamoyl groups, NPK-1868, NPK-1867 and NPK-1886, were studied comparatively for their cardiovascular effects. In three experimental models in hypertensive rats, the hypotensive potency of these three compounds, given p.o., was almost the same as that of nifedipine and felodipine. However, in anesthetized beagle dogs, the effect of i.v. NPK-1886 was longer-lasting and more selective on vertebral blood flow than that of the other compounds. In pharmacokinetic studies, NPK-1868, given p.o., showed the highest Cmax, and NPK-1868 and NPK-1886 showed a longer half-life than felodipine. These data suggest that NPK-1886 is a potent hypotensive substance that has a longer-lasting effect on cerebral blood flow.

Anesthesia↗