Interactions of selective serotonin reuptake inhibitors with subtypes of sigma receptors in rat brain.
Experiments were conducted to determine whether in ovo injection of Flutamide, a non-steroidal anti-androgen, would affect posthatching growth of broiler chickens. Before doing these studies it was necessary to develop a bioassay to demonstrate that Flutamide had anti-androgenic actions when injected in ovo. In ovo injection of 0.06 to 1.74 mumol of testosterone propionate (TP) per egg on the 8th d of incubation caused a dose-related decrease in weight of the bursa of Fabricius of newly hatched chicks. In subsequent experiments, 1.74 mumol of Flutamide significantly decreased the bursal regression produced by 0.58 mumol of TP when both substances were injected on Day 8 of incubation and bursal weights were taken on the day of hatch. Having established that Flutamide could block the effects of high doses of exogenous TP, it was reasoned that it could block the action of much lower endogenous levels. In two of the three experiments, injection of Flutamide on the 8th d of incubation resulted in a dose-related decrease in 21- and 49-d BW of male broiler chickens. The material had no effect on BW of males in one experiment and had no effect on BW of females at any age in any of the experiments. The data suggest that interference with the actions of endogenous androgens during embryonic life suppresses the posthatching growth of male broilers.
This article provides a summary of the pharmacodynamic properties of major antiandrogens as well as an extensive review of their tolerability. Presently there are two classes of androgen receptor antagonists: the so-called pure, non-steroidal antiandrogens which include flutamide, nilutamide and the more recent bicalutamide and the steroidal antiandrogens cyproterone acetate, megestrol acetate and WIN 49596. Although non steroidal and steroidal compounds have been found to be equally effective in the treatment of prostate cancer presently no studies comparing the use of steroidal or non steroidal antiandrogens with chemical or surgical castration have evaluated quality of life per se. The only advantage of cyproterone acetate on pure antiandrogens seems to be the low incidence of hot flushes; a commonly reported adverse effect of androgen ablative therapy. However, hepatotoxicity associated with long term daily doses of 300 mg daily and the unacceptably high incidence of cardiovascular side effects (10%) should restrict its use to patients who are intolerant of pure antiandrogen compound. In contrast to steroidal compound nonsteroidal compounds let sexual potency to be retained, which is an important consideration with respect to the quality of life of some patients and, at present, the main indication for monotherapy with the pure antiandrogens. As regard as pure antiandrogens clinically important adverse events including gastrointestinal events, particularly diarrhea and occasional disturbances of liver function related to flutamide treatment and antabuse effect, problems with light-dark adaptation and rare interstitial pneumonitis related to nilutamide indicates the bicalutamide, due to its better tolerability profile, together with its once-daily oral administration regimen, could be considered the antiandrogen of first choice in the treatment of prostatic cancer.
Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective.
Gubernacula from male Sprague-Dawley control (n = 22) and flutamide-treated (n = 18) rats at E17, E19, and D0 time-points were processed for immunohistochemistry. Sagittal sections stained for presence of androgen receptor, Axin2, and β-catenin were analyzed by fluorescent confocal microscopy.
This prospective study applied triple blind method, a simple convenience sampling method, to induce ovulations of the ninety six PCOS patients. Patients were divided into two groups; group A included 53 subjects (received Flutamide + Clomiphene Citrate) and group B included 43 subjects (received placebo + Clomiphene Citrate). Ultrasound was carried to determine the size of follicles and growth rate of them during follicular phase of the menstrual cycle. Also, progesterone levels were measured on days 19 and 21 of the menstrual cycle.
1. Effects of two doses of cyproterone acetate (CA) and flutamide (FLU) (50 and 100 mg/kg/3 days) on the testicular steroidogenesis in male rats have been investigated, by measuring the content of cytochrome P-450, cytochrome b5 and cytochrome c reductase activity in the microsomal fraction. 2. CA provoked a significant decrease in cytochrome P-450 content while FLU induced an increase with the lowest dose but a significant decrease after administration of 100 mg/kg. 3. On the other hand, in all cases the cytochrome b5 and cytochrome c reductase activity remained unchanged. 4. The plasma levels of LH and testosterone were measured after CA and FLU injection (50 and 100 mg/kg/3 days). 5. CA administration provoked a reduction in blood levels of these hormones while FLU induced a significant increase in both. 6. These data suggested that CA and FLU modified the cytochrome P-450 in rat testes by an indirect mechanism, probably through the modification of LH plasma levels.