Triparanol

Chlorobenzyl chloride Ambenonium chloride Ticlopidine HCI p-Chlorobenzyl chloride Clobutinol Echonazole nitrate Indomethacin Pyrrobutamine Triparanol... 

In a prospective study even in low doses (for example 10 mg/day or lower) tamoxifen caused ocular toxicity if given for a sufficiently long period most of the changes were reversible but they justify very close monitoring (44). A related compound, MER-29 (triparanol), causes cataract and has various other adverse reactions in common with tamoxifen. 

Triparanol, the first inhibitor candidate in the clinic, interferes late in the metabolic pathway and was withdrawn quickly owing to side effects. In contrast, the... 

In Chlorella species triparanol inhibited the removal of the 14a-methyl group, the second alkylation of the side-chain, and, in one species, the A8- A7-isomerase.149 This drug and AY9944 showed a lack of specificity in Chlorella, and it may be that primitive plants like these might be valuable as test organisms to establish the activities of potential inhibitors of sterol biosynthesis. 

The exact mechanism for this dermopathy is unknown, but it has been speculated that kava may interfere with cholesterol metabolism, leading to a reversible, acquired ichthyosis similar to that seen with the use of lipid-lowering agents such as triparanol (3). Skin biopsies of two recent cases associated with use of the commercially available product have revealed lymphocytic attacks on sebaceous glands, with subsequent destruction and necrosis caused by CD8+ cells (see Section 5) (26). Yet another theory involves interference with B vitamin metabolism or action (27). 

The triparanol experience was an unfortunate but sobering event. The drug, which was developed in the late 1950s, effectively lowered cholesterol levels by inhibiting the final step reduction of the 24-25 double bond of desmosterol to yield cholesterol. 

The regulatory function of this enzyme at such an early phase in the cholesterol synthesis, and the findings that a defect in this regulation exists in FH patients, rekindled interest in this enzyme as a target for cholesterol inhibition after years of hands off because of the triparanol experience. 

Svoboda and co-workers (Svoboda and Robbins, 1967 1968 Svoboda et al., 1967 1969) found that triparanol, 2-(4-chlorophenyl)-l-[4-(2-diethylamino-ethoxy)phenyl]-l-(4-tolyl) ethanol and 22,25-diazacholesterol (99) inhibit sterol reductase and also disrupt the normal growth and development of the larvae of tobacco homworm, Manduca sexta. Both compounds are known as inhibitors of steroid biosynthesis in vertebrates. 22,25-DiazacholesteroI is a hypocholeste-rolaemic agent acting as a competitive antagonist of cholesterol. A similar activity was found later for 25-azacholesterol (100). For the determination of the minimum structural requirements of activity, Svoboda and Robbins synthesised and tested... 

Roux C., Action teratogene du triparanol chez fanimal, Archives fran aises de pediatrie 21 (1964) 451 64. 

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