Identification of 24-dehydrocholesterol in the serum of patients treated with MER-29

Effects of Triparanol (Mer-29) on Cholesterol Biosynthesis and on Blood Sterol Levels in Man*

“…Animal studies in this laboratory demonstrated the accumulation of desmosterol (24-dehydrocholesterol) in the tissues of MER-29-treated animals, and a series of isotopic studies established that the major site of action of the drug was at the last step in cholesterol biosynthesis-namely, in the reduction of desmosterol to cholesterol (1,15,16). The present paper reports clinical studies which show that the mechanism of action in man is similar to that in animals.…”

“…Although only a few patients are available for comparison, it is of interest to note that there appeared to be no strikingly different response in patients on a diet devoid of cholesterol than in the patients receiving exogenous cholesterol (1).…”

“…After saponification in methanolic KOH, the sterols were extracted with heptane, washed with water and divided into two aliquots for counting of radioactivity and for calorimetric determination of cholesterol and desmosterol. Knowing the analytical values for the two sterols in the samples counted, it was possible to calcu- 1 The authors wish to thank Dr. E. Mosettig and Mr. R. T. Brown for preparing the synthetic material. late the two specific radioactivities individually, even though the desmosterol was contaminated with a small amount of cholesterol and vice versa.…”

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part V: The discovery of the statins and the end of the controversy

“…Knowing the site of inhibition led to a number of findings that challenged the value of triparanol. For example, it was shown that large amounts of desmosterol accumulated in the plasma of treated animals and patients, accounting for up to 30% of total plasma sterols (19). A key point of confusion was that the color yield of desmosterol in the then standard LiebermannBurchard reaction was approximately half that of cholesterol.…”

Sur quelques propriétés biologiques d’un analogue fluoré du triparanol

“…Un des médicaments les plus souvent préconisés à l'heure ac tuelle pour combattre l'hypercholestérolémie est le triparanol (Mer 29®), lequel est, chimiquement parlant, le p-chlorobenzyl p-tolyl-[p-(/?-diéthylaminoéthoxy)phényl]carbinol ; on sait que ce com posé, de formule (I), possède la propriété d'interrompre la bio synthèse du cholestérol par les organismes animaux au stade du desmostérol, la conversion de ce dernier corps en cholestérol luimême étant inhibée (1). Bien que les effets biologiques d'une accu mulation de desmostérol dans l'organisme ne soient pas encore connus, et que, par ailleurs, la présence de ce stéroïde dans les plaques d'athérome ait été constatée par divers auteurs, des résul tats cliniques favorables ont néanmoins été obtenus avec le tri paranol (2) ; de ce fait, il était intéressant de préparer des subs tances dont la structure moléculaire serait suffisamment voisine de celle du triparanol pour justifier le recherche d'une activité hypocholestérolém iante possible.…”