Disease relevance of ETHAMOXYTRIPHETOL

• MER-25 is antiestrogenic in primates and was investigated in the clinics in a wide range of gynecological conditions, including breast and endometrial cancer [1].
• In the in vivo carrageenan-induced rat paw edema studies, diethylstilbestrol was more potent as an anti-inflammatory agent than was clomiphene, and ethamoxytriphetol and triparanol were only marginally effective [2].
• The MER-25-treated rats showed higher levels of lordosis behaviour than oil-treated rats in all four treatment groups [3].
• Serum P production rates (metabolic clearance rate [MCR] x peripheral serum concentration) were determined in baboons prior to and following maternal administration of the antiestrogen ethamoxytriphetol (MER-25) at 30, 15, 6, or 3 mg/kg of body weight by mouth daily for 10 or 20 day periods during or throughout the last one third of gestation [4].
• The MER-25 causes decreases in eating and weight gain that are not due to toxicity, as indicated by its failure to induce a learned aversion to saccharin and by its failure to alter spontaneous activity [5].

Psychiatry related information on ETHAMOXYTRIPHETOL

• The MER-25 did not affect the running of castrated, oil-treated male rats and did not inhibit the running induced by food deprivation [6].

High impact information on ETHAMOXYTRIPHETOL

• Similarly, administration of the estrogen antagonist MER-25 to intact animals in the last trimester had no effect on maternal serum inhibin concentrations [7].
• We examined this possibility in the present study by determining the effects of ACTH and estrogen on DHA formation by adrenal cells of fetuses obtained from baboons at mid- and late gestation and from animals administered the antiestrogen MER-25 throughout late gestation [8].
• Adrenals were removed from baboon fetuses on day 100 (midgestation; n = 7) and day 170 (late gestation; n = 6; term, day 184) of gestation from untreated animals and on day 170 from fetuses whose mothers were treated with MER-25 on days 140-170 (25 mg/kg BW.day; n = 7) [8].
• P-450scc activity, as determined by formation of pregnenolone (P5) and P4 during a 30-min incubation (picomoles per mg protein), was 37% lower (P less than 0.01) in placental mitochondria obtained from MER-25-treated baboons (179.8 +/- 25.0) than in that from untreated (285.4 +/- 13.4) baboons [9].
• In the present study, increasing amounts of the anti-estrogen 1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenoletha nol (MER-25) were administered to pregnant baboons (Papio anubis) to block the action of endogenous estrogen and to determine effect on placental low-density lipoprotein (LDL) uptake [10].

Chemical compound and disease context of ETHAMOXYTRIPHETOL

• All doses of MER-25 caused significantly more lordosis behaviour after oestrogen and progesterone than did injections of oil [11].

Biological context of ETHAMOXYTRIPHETOL

• To examine this possibility, the conversion of [3H]P5 to [3H]P4 was determined by the constant infusion method on day 100 (midgestation) and day 175 (near term) of gestation in baboons that received MER-25 (25 mg/day X kg BW, po) on days 95-100 or 140-175 (term = 184 days) [12].
• MER-25 had no effect on either the cervicovaginal epithelium or ovarian histology [13].
• Luteal function in baboons with administration of the antiestrogen ethamoxytriphetol (MER-25) throughout the luteal phase of the menstrual cycle [14].
• The relative binding affinities (RBA) of TAM, 4-OH-TAM, and MER-25 to mouse uterus estrogen receptor (ER) and mouse liver antiestrogen binding sites (AEBS) were compared to determine whether either (or both) of these sites mediate the biological effects of these compounds [15].
• Effects of an antioestrogen (MER-25) on sexual and mammary gland morphogenesis of the mouse fetus [16].

Anatomical context of ETHAMOXYTRIPHETOL

• Male rats were treated daily with oil or 100 micrograms of the antioestrogen, ethamoxytriphetol (MER-25), for the first 10 days of life and, when adult, lesions were made in the suprachiasmatic nuclei (SCN) of the hypothalamus or control lesions were made above the SCN and the rats were tested for sexual behaviour [17].
• For adipose tissue LPL activity, both nafoxidine and MER-25 were full estrogen agonists and without antiestrogenic activity [18].
• Effects of prostaglandins E2 and F2alpha (PGE2; PGF2alpha), trilostane, mifepristone, palmitic acid (PA), indomethacin (INDO), ethamoxytriphetol (MER-25), PGE2 + PA, or PGF2alpha + PA on PGE2, PGF2alpha, and progesterone secretion by bovine corpora lutea of mid-pregnancy in vitro [19].

Associations of ETHAMOXYTRIPHETOL with other chemical compounds

• Four of the MER-25-treated baboons received no other treatment, and four had the corpus luteum of pregnancy surgically excised between days 104 and 118 of gestation [20].
• Diethylstilbestrol, clomiphene, ethamoxytriphetol and triparanol were 0.18, 1.0, 0.02 and 0.01 times as potent in the in vitro inhibition of prostaglandin synthetase, respectively as was indomethacin [2].
• These data suggest that differences in the biological actions of tamoxifen and MER-25 in mice are not mediated through AEBS and are most likely due to differences in their interactions with ER [15].
• Oral administration of the estrogen antagonist MER-25 at two dosage levels (15 and 30 mg/kg/day) to the pregnant baboon from days 35 to 55 after conception results in a decline in peripheral plasma levels of progesterone within a few days and persists for at least 20 days after the termination of treatment with no effect on plasma estradiol levels [21].
• Ethamoxytriphetol, MER-25, which antagonizes many estrogen-dependent effects but which mimics the action of EB on food intake, also led to decreases in ethanol consumption that paralleled those reported for food intake [22].

Analytical, diagnostic and therapeutic context of ETHAMOXYTRIPHETOL

• Under each of these endocrine conditions, except after castration alone, the MER-25-treated rats showed a reduced capacity to ejaculate [3].

References