Studies of cholesterol biosynthesis. I. The identification of desmosterol in serum and tissues of animals and man treated with MER-29.

The compound (1-[p-@-diethy aminoethoxy)-phenyl]-l-(ptolyl)-2-(p-chlorophenyl)ethanol), known by its trade name as MER-29,’ has been shown by Blohm et al. to cause a depression in serum and tissue cholesterol and to inhibit cholesterol biosynthesis in animals (1,2). These authors found that the incorporation of I-C14-acetate into the total nonsaponifiable lipid fraction of rat liver and into the total digitonin-precipitable sterol fraction was not affected by the drug. However, these authors found that on purification of this fraction through the dibromide, most of the radioactivity proved to be in sterols other than cholesterol. The present studies were undertaken in an attempt to elucidate the mechanism of action of MER-29 on cholesterol biosynthesis. The experiments reported here establish desmosterol (24-dehydrocholesterol) as a major sterol component in the serum, in the liver, and in other tissues of animals treated with MER-29. A calorimetric method for the determination of desmosterol in the presence of cholesterol is described and tissue levels in treated animals are reported. Finally, some general observations of the effects of MER-29 on weight gain and on serum and liver lipid levels are presented. Preliminary reports of some of these results have appeared elsewhere (3).