Mer-29 - 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. 

The best known compound in the triarylethanol series is the hypocholesterol-emic agent, triparanol (Mer. 29, XXXVI) [133, 134]. This drug effectively reduced serum cholesterol levels in patients with atherosclerotic diseases and in various states of hyperlipemia. As in the cases of the basic ethers XXI and XXXI, triparanol inhibited the biosynthesis of cholesterol mainly at the last step, by blocking the reduction of 24-dehydrocholesterol (desmosterol) to cholesterol. In the rat the plasma concentration of desmosterol is very low. Treatment of rats with triparanol led to an accumulation of desmosterol in the serum and in eight tissues [135]. Triparanol also caused desmosterol accumulation in man [136]. 

Again in the 1950s, triparanol (MER-29) was introduced as a drug to reduce blood cholesterol in patients with hypercholesterolaemia. It was withdrawn from clinical use in April 1962. In addition to skin lesions, loss of hair and libido, the main ocular side-effect in man associated with the oral application of this drug was the formation of anterior and posterior subcapsular cataracts, in general, with a latency of 8 - 9 months (Laughlin and Carey, 1962). Retrospectively, cataracts were reproduced within 3 months in rats (v. Sallmann et al., 1963) and within 5-7 months in dogs, but not in monkeys (Bellows, 1963). 

Achor, R. W. P., Winkelmann, R. K. and Perry, H. O. (1961). Cutaneous side effects from use of triparanol (Mer 29) Preliminary data on ichthyosis and loss of hair. Proc. Mayo Clin., 36,211... 

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