Selective estrogen receptor modulators raloxifene

Liu, H. Qin,Z. Thatcher, G. R. Bolton, J.L. Uterine peroxidase-catalyzed formation of diquinone methides from the selective estrogen receptor modulators raloxifene and desmethylated arzoxifene. Chem. Res. Toxicol. 2007, 20, 1676-1684. 

Simoncini T, Genazzani AR, Liao JK (2002a) Nongenomic mechanisms of endothelial nitric oxide synthetase activation by the selective estrogen receptor modulator raloxifene. Circulation 105 1368-1373... 

Blum A, Hathaway L, Mincemoyer R, Schenke WH, Casco G, Waclawiw M A, Panza MA, Cannon III RO (2000) Hormonal, lipoprotein, and vascular effects of the selective estrogen receptor modulator raloxifene in hypercholesteronomic men. Am J Cardiol 85 1491-1494... 

Buelke-Sam J, Bryant HU, Francis PC (1998) The selective estrogen receptor modulator, raloxifene an overview of nonclinical pharmacology and reproductive and developmental testing. Reprod Toxicol 12 217-221... 

Taranta A, Brama M, Teti A, De 1, V, Scandurra R, Spera G, Agnusdei D, Termine JD, Migliaccio S (2002) The selective estrogen receptor modulator raloxifene regulates osteoclast and osteoblast activity in vitro. Bone 30 368-376... 

Blum A, Schenke WH, Hathaway L, Mincemoyer R, Csako G, Waclawiw MA, Cannon RO III (2000) Effects of estrogen and the selective estrogen receptor modulator raloxifene on markers of inflammation in postmenopausal women. Am J Cardiol 86 892-895... 

Selzman CH, Turner AS, Gaynor JS, Miller SA, Monnet E, Harken AH (2002) Inhibition of intimal hyperplasia using the selective estrogen receptor modulator raloxifene. Arch Surg 137 333-336... 

Zuckerman SH, Bryan N (1996) Inhibition of LDL oxidation and myeloperoxidase dependent tyrosyl radical formation by the selective estrogen receptor modulator raloxifene (LY139481 HCL). Atherosclerosis 126 65-75... 

Fig. 1 A deviation of only 20° in the dihedral of the selective estrogen receptor modulator raloxifene would result in a change of 2.5 A in the tertiary amine position, missing the favorable hydrogen-bond interaction with Asp351...

Figure 6-12 Bioactivation and competing detoxication pathways of the selective estrogen receptor modulator raloxifene.

Treatment of osteoporosis depends on the cause. In secondary osteoporosis, treatment is directed at the underlying condition. Most therapies for the treatment of postmenopausal osteoporosis are directed at decreasing osteoclastic bone resorption. Antiresorptive therapies include bisphosphoiiates (alendronate and risedronate), estrogen replacement, selective estrogen receptor modulators (raloxifene), and calcitonin (nasal spray or injection). The FDA has recently approved recombinant hPTH(l-34) (injection), the first approved therapy for stimulating bone formation. 

H. Ogita, K. Node, H. Asanuma, S. Sanada, Y. Liao, S. Takashima, M. Asakura, H. Mori, Y. Shinozaki, M. Hori and M. Kitakaze, Amelioration of ischemia and reperfusion induced myocardial injury by the selective estrogen receptor modulator, raloxifene, in the canine heart, J. Am. Coll. Cardiol. 40,998-1005 (2002). 

Calcitonin therapy results in decreased bone resorption. Osteoclasts have calcitonin receptors and calcitonin inhibits their activity. Sodium fluoride stimulates bone formation by unknown mechanisms. In women with osteoporosis, fluoride therapy produced an increased bone mineral density but no reduction in the rate of vertebral fractures. Other drugs known as selective estrogen receptor modulators (raloxifene, droloxifene, idoxifene, and levormeloxifene) may provide an alternative to estrogen replacement therapy (Chapter 34). Administration of low doses of PTH [or recombinant PTH( 1 -34)] does not affect serum calcium concentration, promotes bone formation, and increases mineral density. This anabolic action of PTH is probably mediated by decreasing osteoblast apoptosis. 

Selective Estrogen Receptor Modulators Raloxifene (EVISTa) acts as an estrogen agonist on bone and liver, is inactive on the uterus, and acts as an estrogen antagonist on the breast. In postmenopausal women, raloxifene modestly increases bone mineral density and has been shown to reduce the risk of vertebral compression fractures in this setting, it is approved for both the prevention and treatment of osteoporosis. The major adverse effect is worsened vasomotor symptoms the drug also increases the incidence of deep venous thrombosis. 

Selective estrogen receptor modulators (SERMs) are synthetic compounds with partially agonistic and partially antagonistic estrogenic properties. In bone, SERMs inhibit bone resorption via the mechanisms known for estrogens. Major SERMs are tamoxifen, a triphenylethylene compound, and raloxifene. In postmenopausal women, the latter has been shown to prevent bone loss and to reduce fracture risk by 40%. 

Baker VL, Draper M, Paul S, Allerheiligen S, Giant M, Shifren J, Jaffe RB (1998) Reproductive endocrine and endometrial effects of raloxifene hydrochloride, a selective estrogen receptor modulator, in women with regular menstrual cycles. J Clin Endocrinol Metab 83 6-13... 

Cheng WC, Yen ML, Hsdu SHJ, Chen KH, Tsai KS (2004) Effects of raloxifene, one of the selective estrogen receptor modulators, on pituitary-ovary axis and prolactin in postmenopausal women. Endocrine 23 215-218... 

Doran PM, Riggs BL, Atkinson EJ, Khosla S (2001) Effects of raloxifene, a selective estrogen receptor modulator, on bone turnover markers and serum sex steroid and lipid levels in elderly men. J Bone Miner Res 16 2118-2125... 

Muchmore DB (2000) Raloxifene a selective estrogen receptor modulator (SERM) with multiple target system effects. Oncologist 5 388-392... 

Nickelsen T, Lufkin EG, Riggs BL, Cox DA, Crook TH (1999) Raloxifene hydrochloride, a selective estrogen receptor modulator safety assessment of effects on cognitive function and mood in postmenopausal women. Psychoneuroendocrinology 24 115-128... 

Aromatase inhibitors (including anastrozole, letrozole, aminoglutethimide, exemestane, formestane, testolactone), selective estrogen receptor modulators—SERMs (including raloxifene, tamoxifen, toremifene), clomiphene, cyclofenil, fulvestrant Diuretics, amiloride, bumetanide, canrenone, chlorthalidone, etacrynic acid, furosemide, indapamide, metolazone, spironolactone, thiazides, triamterene... 

Raloxifene (Evista) [Selective Estrogen Receptor Modulator]... 

Heringa M. Review on raloxifene profile of a selective estrogen receptor modulator. Int J Clin Pharmacol Ther 2003 41 331 15. 

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