Antiestrogens tamoxifen

Fan, P. W. Zhang, F. Bolton, J. L. 4-Hydroxylated metabolites of the antiestrogens tamoxifen and toremifene are metabolized to unusually stable quinone methides. Chem. Res. Toxicol. 2000, 13, 45-52. 

O Regan RM, Cisneros GM, England GM, MacGregor JI, Muenzner HD, Assikis VJ, et al. (1998) Effects of the antiestrogens tamoxifen, toremifene, and ICI 182,780 on endometrial cancer growth. J Natl Cancer Inst 90 1552-1555... 

Greenberg DA, Carpenter CL, Messing RO (1987) Calcium channel antagonist properties of the antineoplastic antiestrogen tamoxifen in the PC12 neurosecretory cells. Cancer Res 47 70-74... 

Liu XK, Katchman A, Ebert SN, Woosley RL (1998) The antiestrogen tamoxifen blocks the delayed rectifier potassium current, IKr, in rabbit ventricular myocytes. J Pharmacol Exp Ther 287 877-883... 

Grey AB, Stapleton JP, Evans MC, et al. (1995) The effect of antiestrogen Tamoxifen on bone mineral density in normal late postmenopausal women. Am J Med 99 636-641... 

Cronan T, Conrad J, et al (1985) Effects of chronically administered nicotine and sahne on motor activity in rats. Pharmacol Biochem Behav 22(5) 897-899 Curtis L, Buisson B, et al (2002) Potentiation of human alpha4beta2 neuronal nicotinic acetylcholine receptor by estradiol. Mol Pharmacol 61(1) 127-135 Dalton JC, Vickers GJ, et al (1986) Increased self-administration of cocaine following haloperidol sex-dependent effects of the antiestrogen tamoxifen. Pharmacol Biochem Behav 25(3) 497-501 Damsma G, Day J, et al (1989) Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens. Eur J Pharmacol 168(3) 363-368 Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85(14) 5274-5278... 

Paul R, et al. (1998) Both the immunosuppressant SR31747 and the antiestrogen tamoxifen bind to an emopamil-insensitive site of mammalian Delta8-Delta7 sterol isomerase. J. Pharmacol. Exp. Then 285 1296-1302. 

The gynecological consequences of antiestrogens (tamoxifen and toremifene) have been evaluated in 167 postmenopausal breast cancer patients in a 3-year prospective study. There was a proliferative endometrium more often in the tamoxifen group than in the toremifene group, but this did not translate into an increase in the rate of endometrial cancer. The authors did not recommend routine surveillance of the endometrium. 

Robertson DW, Katzenellenbogen JA (1982) Synthesis of the E and Z isomers of the antiestrogen tamoxifen and its metabolite, hydroxytamoxifen, in the tritium-labeled form. J Org Chem 47 2387-2393... 

The ability of cyclodextrin to resolve stereoisomers is very readily applied for the separation of diastereomers, such as the cis- and trans-geometric isomers (6,7). Similar to both of the examples presented above, resolution of geometric isomers appears to result from both the level of inclusion complex formed, as well as the level of interaction of the molecule with the 2- and 3-hydroxyl groups of the cyclodextrin. This can be illustrated with the synthetic antiestrogen tamoxifen (Figure 1), which is synthesized in both the cis and trans forms. 

Grey, A.B., Stapleton, J.P., Evans, M.C. and Reid, I.R. (1995) The effect ofthe antiestrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women. The Journal of Clinical Endocrinology and Metabolism, 80, 3191-3195. 

Chander, S.K., McCague, R., Luqmani, Y., Newton, C., Dowsett, M., Jarman, M. and Coombes, R.C. (1991) Pyrrolidino-4-iodotamoxifen and 4-iodotamoxifen, new analogues of the antiestrogen tamoxifen for the treatment of breast cancer. Cancer Research, 51, 5851-5858. 

This may be especially attractive to persons carrying known cancer-susceptibility genes. The S5mthetic antiestrogen tamoxifen is being evaluated as a chemopreventive agent for breast cancer. However, a planned large-scale trial was postponed because of uncertainities about safety. ... 

Oncologists make use of this specific antiestrogen, tamoxifen, in depriving the malignant process of the source of these hormones, therefore, shows a much better, safer and potentially useful method of treatment. 

Tamoxifen. The antiestrogen, tamoxifen, is a cationic amphiphilic drug which is electrophoretically transported into the mitochondrial matrix where it reaches high concentrations that directly inhibit both mitochondrial p-oxidation and mitochondrial respiration, and also deplete mtDNA in mice, as mentioned above (Larosche et al. 2007). 

Antiestrogens Tamoxifen, toremifene, fulvestrant Alt, D , En , G Acute toxic effects unlikely. Tremors, hyperieflexia, unsteady gait, QT prolongation with high doses of tamoxifen. 

Scheme 1.9 The antiestrogen tamoxifen 16, its active metabolite hydroxy tamoxifen 17 and hydroxy ferrocifens 18.

The development of the MCF-7 cell line, as well as others, ushered in a busding period of research to unlock the mechanisms of estrogen-based carcinogenicity. In 1975, scientists demonstrated that the antiestrogen tamoxifen inhibited the growth of MCF-7 cells. This finding had profound implications, as tamoxifen, which competes with estradiol to bind to the estrogen receptor, subsequently went on to become a standard component of therapy for virtually... 

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