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The decanoates of flupenthixol and clopenthixol in the treatment of chronic schizophrenic in-patients. Implications for community psychiatry.

Vagrant chronic schizophrenic subjects in a stable untreated state received in-patient treatment with either Flupenthixol decanoate or Clopenthixol decanoate. Both drugs were found to be significantly effective and well tolerated. The apparent better response to Flupenthixol decanoate was seen as dose-dependent. The findings and their implications for Community Psychiatry, particularly in developing countries are discussed.

Adult↗

Reduced haloperidol/haloperidol ratios after oral haloperidol and decanoate administration in schizophrenics.

1. Haloperidol and reduced haloperidol plasma concentrations were measured in thirteen stable schizophrenic patients that received both oral haloperidol and haloperidol decanoate. 2. Significant correlations between reduced haloperidol/haloperidol ratios from oral haloperidol and haloperidol decanoate occurred at week two and week 16, respectively. 3. The formation of RH was consistent during haloperidol decanoate treatment.

Administration, Oral↗

[Bromperidol decanoate in the residual phase of schizophrenia].

We assessed the safety and therapeutic efficacy of bromperidol decanoate in a six-month open trial on 21 patients (13 males and 8 females), mean age 41.3 years, who were no longer in the acute phase and were being treated as outpatients. The recommended initial dosage was 150 mg bromperidol (one 3 ml ampoule), and this did not in fact have to be increased during the trial. The scores for psychotic symptom rating scales (SAPS, SANS, BPRS, HAM-D and social adaptation scale) were analysed by analysis of variance, which indicated that bromperidol decanoate was effective on almost all parameters. Adverse reactions were reported for 14.3% of the patients, indicating that the drug was very well tolerated; only three patients complained of a total of seven adverse events. In conclusion, bromperidol decanoate was effective in the treatment of residual schizophrenia, with significant differences between before and after treatment ratings for symptoms. The drug was well tolerated, only one patient dropping out on account of adverse reactions.

Adolescent↗

Clopentixol decanoate in the treatment of chronic alcoholism.

The treatment of alcoholism still presents great problems because a number of factors have to be taken into consideration. Tranquilizers and chlormethiazol are only justified in the detoxication phase. For the subsequent after-care, depot neuroleptics are recommended because of the uniformly high plasma level. We gave clopentixol decanoate - 100 mg i.m. - in two-weekly intervals. The symptoms caused by ethylism were adequately overcome without side effects. Clopentixol decanoate creates the basis for successful psychotherapy: only when the mood situation is compensated and the internal unrest overcome can verbal therapy be successful.

Adult↗

Cell binding and growth inhibition by hexachlorophene of decanoate and their reversibility.

More than 80% of the hexachlorophene added to a Bacillus subtilis culture binds to the cells. Complete growth inhibition requires 6 x 10(5) molecules bound per cell. In contrast, more than 99% decanoate remains in solution and 3.8 x 10(7) molecules bound per cell are needed to inhibit growth. Centrifugation and resuspension of cells in growth medium removes only decanoate, whereas the addition of 1% bovine serum albumin to the growth medium removes both inhibitors from their binding sites on the cells. The addition of untreated cells to a hexachlorophene-treated culture enables the hexachlorophene molecules to redistribute among all the cells with the result that the inhibited cells can resume growth.

Bacillus subtilis↗

Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss: a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Weight loss is associated with accelerated mortality and disease progression in patients with human immunodeficiency virus (HIV) infection. Although studies have examined a variety of anabolic therapies in HIV-infected men, the safety and efficacy of such treatments in women have not been adequately studied. METHODS: In this randomized, double-blind, placebo-controlled, multicenter, phase I/II study, 38 HIV-infected women with documented weight loss of 5% or greater in the preceding year or a body mass index of less than 20 kg/m(2) were randomized to receive nandrolone decanoate (100 mg) or an equivalent volume of placebo every other week by intramuscular injection. Subjects received blinded treatment for 12 weeks, followed by open-label therapy for 12 weeks. Lean body mass and fat (bioelectrical impedance analysis) and weight were measured at baseline and at weeks 6, 12, 18, and 24. Biochemical assessments of safety (hematologic analyses, liver function tests, and sex hormone measurements) were performed at these same time points. Clinical signs and symptoms were monitored biweekly. RESULTS: Subjects randomized to receive nandrolone had significant increases in weight and lean body mass during blinded treatment (4.6 kg [9.0%] and 3.5 kg [8.6%], respectively; P<.001 vs baseline and placebo in each case). Fat mass did not change statistically significantly in either group. Although there were no statistically significant differences between groups in biochemical measures, the number of grade 3 or greater toxicities, or reports of virilizing effects, a full assessment of safety cannot be made in a trial of this size. CONCLUSION: Nandrolone decanoate therapy may prove to be generally safe and beneficial in reversing weight loss and lean tissue loss in women with HIV infection and other chronic catabolic diseases.

Adult↗

Anabolic effects of nandrolone decanoate in patients receiving dialysis: a randomized controlled trial.

CONTEXT: Patients receiving dialysis commonly experience malnutrition, reduced muscle mass (sarcopenia), and fatigue for which no effective treatment has been identified. Anabolic steroids are known to increase muscle mass and strength in healthy individuals, but their effect on the sarcopenia and fatigue associated with long-term dialysis has not been evaluated. OBJECTIVE: To assess the effects of an anabolic steroid, nandrolone decanoate, on lean body mass (LBM), functional status, and quality of life in dialysis patients. DESIGN: Randomized, double-blind, placebo-controlled trial conducted between April 1996 and July 1997. SETTING: Hospital-based outpatient dialysis unit. PATIENTS: Twenty-nine patients undergoing dialysis for at least 3 months. INTERVENTION: Nandrolone decanoate, 100 mg (n = 14), or placebo (n = 15) by intramuscular injection once a week for 6 months. MAIN OUTCOME MEASURES: Weight, LBM, fatigue, grip strength, walking and stair-climbing times, and treadmill performance after 3 and 6 months of treatment. RESULTS: Lean body mass increased significantly in patients given nandrolone compared with patients given placebo (mean change [SD], +4.5 [2.3] kg; P<.001 compared with baseline). This effect was significantly greater than the change in LBM in the placebo group (mean change [SD], +1.9 [1.6] kg; P = .003 compared with baseline; P = .005 compared with nandrolone group). Serum creatinine levels increased in the nandrolone group (+168 [203] mmol/L [1.9 [2.3] mg/dL]; P = .02) but not in the placebo group (-4.0 [177] mmol/L [0.04 [2.0] mg/dL]; P = .95), suggesting an increase in muscle mass. Time to complete the walking and stair-climbing test decreased from 36.5 to 32.7 seconds in the nandrolone group, while those in the placebo group increased from 38.7 to 42.1 seconds (P = .05). Peak oxygen consumption increased in the individuals in the nandrolone group who performed treadmill tests, but not to a statistically significant degree. Grip strength did not change in either group. CONCLUSIONS: Treatment with nandrolone for 6 months resulted in a significant increase in LBM associated with functional improvement in patients undergoing dialysis.

Absorptiometry, Photon↗

Calcium-deficient diet in ovariectomized dogs limits the effects of 17 beta-estradiol and nandrolone decanoate on bone.

Postmortem measurements by dual-photon absorptiometry of the femur and the second lumbar vertebra in adult dogs indicated bone loss after ovariectomy, which was more pronounced when calcium-deficient diet was given in ovariectomized dogs. This bone loss was nonhomogeneous throughout the femur. Ovariectomy resulted in trabecular and cortical bone loss, and additional calcium-deficient diet resulted in a further highly significant trabecular bone loss at the proximal epiphysis of the femur and in the vertebra. This bone loss was presumably the result of increased bone turnover, as reflected by the highly significant increase in serum alkaline phosphatase. Estrogens could only partially prevent the bone loss induced by calcium deficiency after ovariectomy, and nandrolone decanoate was not effective. We conclude that (1) ovariectomy results in bone loss in adult dogs, (2) this bone loss is more pronounced after calcium-deficient diet, (3) calcium deficiency could be a limiting factor for the preventive effect of estrogens and nandrolone decanoate, and (4) dual-photon absorptiometry allows the evaluation of nonhomogeneous bone loss throughout excised bones.

Absorptiometry, Photon↗

Nandrolone decanoate: pharmacological properties and therapeutic use in osteoporosis.

The therapeutic profile on bone of nandrolone decanoate is that of inhibitor of bone resorption with temporary increase in bone formation, followed by an absence of suppression of bone formation, indicating uncoupling of bone resorption and formation. This results is an increase in bone mineral content at the proximal and distal radius, and in some patients at the lumbar spine. Furthermore, nandrolone decanoate increases calcium balance and muscle mass, diminishes vertebral pain and increases the mobility of the spine. Virilization occurred in around 50% of the patients (mainly hoarseness and/or hirsutism), and 9% of the patients dropped out because of this reason. A dose of 50 mg every 3 to 4 weeks is indicated in the treatment of osteoporosis in women, especially when they have low muscle mass, associated debilitating disease, and in patients with corticosteroid induced osteoporosis. It should only be prescribed after the age of 65 to 75 years to minimize the occurrence of clinical adverse effects and to increase its tolerability, which is higher in this group. Although some effects are reported on fracture rate, insufficient prospective data are available.

Aged↗

Asymmetric distribution of decanoate in triacylglycerol synthesized in vitro by mammary glands of lactating mice.

Slices, prepared from the mammary glands of lactating mice, were incubated with either [1-14C]acetate, [U-14C]glucose, or [1-14C]decanoate. From all 3 substrates, radioactivity in the synthesized lipids was found mainly in triacylglycerols (TG). When acetate or glucose served as substrate, decanoate (C10) accounted for 24% of the fatty acids in TG. Hydrolysis of the TG by pancreatic lipase yielded [14C] fatty acids which had relatively more C10 (38%) than did either of the other hydrolysis products mono- or diacylglycerol (14-17%). However, when TG produced by slices from C10 were hydrolyzed, the acid was found to be esterified equally at the C-1, C-2 and C-3 of glycerol. Thus, when fatty acids are synthesized de novo and are converted to TG by gland slices, C10 is predominantly located in the C-3 position, a finding in accord with the situation in milk TG, although such preferential incorporation does not occur when the free acid is presented to the tissue slices.

Animals↗

C6--C10-dicarboxylic aciduria in starved, fat-fed and diabetic rats receiving decanoic acid or medium-chain triacylglycerol. An in vivo measure of the rate of beta-oxidation of fatty acids.

Administration of decanoic acid to rats resulted not only in elevated urinary excretions of the C10-dicarboxylic acid (sebacic acid), but also in highly elevated excretions of the beta-oxidation products C8- and C6-dicarboxylic acids (suberic and adipic acids). Activation of the lipid metabolism by starvation, fat-feeding and experimental diabetes increased the excretions of adipic acid and decreased the excretions of sebacic acid, i.e. the rate of oxidation of fatty acids was correlated to the adipic : sebacic acid ratio in urine. Compared with nondiabetic unstarved rats the adipic : sebacic acid ratio was elevated 2--3-, 8--16-, 5--19-, and 22--88-times in rats which were, respectively, starved for 2 days, 4 days, on a fat-diet for 4 days, and ketotic due to streptozotocin-induced diabetes. All rats with ratios above 10 were ketotic (urinary excretions of 3-hydroxybutyric acid over 500 microgram/mg creatinine) and all rats with ratios below 4 were nonketotic, while ketosis was a variable finding in rats with intermediary ratios. Similar changes in the ratio of excreted dicarboxylic acids were found when medium-chain triacylglycerols were fed instead of decanoic acid.

Acidosis↗

Studies on osteoporosis VII. Effect of 17 beta-hydroxy-4-estren-3-one 17-decanoate on experimental osteoporosis.

Total body neutron activation analysis was employed to measure total calcium in C3H/St (Ha) female mice. Ninety-nine percent of total body calcium is in bone and loss of calcium was used as an index of osteoporosis. Heparin (500 U/kg B.I.D.) treatment for three months resulted in significant osteoporosis. 17 beta-Hydroxy-4-estren-3-one 17-decanoate 1.5 mg/kg or 4 mg/kg twice monthly prevented this heparin accelerated osteoporosis. The results suggest that 17 beta-hydroxy-4-estren-3-one 17-decanoate may be capable of preventing bone loss and partially increasing bone mass in patients exposed to osteoporosis inducing regimens.

Animals↗

The prevention of corticosteroid-induced osteoporosis with nandrolone decanoate.

The effects of nandrolone decanoate (ND; 50 mg IM every three weeks) on calcium metabolism and forearm bone density were studied in a randomized trial in 35 women receiving long-term therapy with corticosteroids (CST) for rheumatic disease. The 17 patients who served as controls were on CST therapy for less years and their bone density was higher. Thus a second control group, pair-matched with the active treatment group for age, duration of CST therapy and bone density, was selected retrospectively. At the end of the 18 months' treatment course with ND, forearm bone density was increased by 5.1% (P less than 0.01) but fell by 11.3% (P less than 0.01) and 6.7% respectively in the first and second control group. The patients on ND differed significantly from both control groups in the changes at 6, 12 and 18 months (P less than 0.01). Urinary excretion of hydroxyproline fell significantly in patients receiving ND, whereas the biochemical indices of bone formation did not change (alkaline phosphatase) or increased (osteocalcin; P less than 0.01). In conclusion, nandrolone decanoate therapy may be used in the prevention of CST-induced osteoporosis. It also seems to exert mild inhibition of bone resorption without affecting or even stimulating bone formation.

Absorptiometry, Photon↗

Encapsulation and retention of decanoic acid in sol-gel-made silicas.

Porous sol-gel-made silica particles are investigated as encapsulation matrices for controlled release of substances in food and pharmaceutical applications. Here the retention performance of an entrapped model flavor, decanoic acid, inside silica matrices made by hydrolysis of tetraethyl orthosilicate (TEOS) is studied. The retention of decanoic acid is measured by gas chromatography and thermogravimetric analysis. The morphology, specific surface area, porosity, and pore size distribution of the particle matrix is controlled by the sol-gel preparation method. During drying, the weakly cross-linked polymers in a slowly hydrolyzing silica gel deform and wrap around flavor molecules, creating a denser gel structure. There the flavor molecules are entrapped more efficiently than in fast-hydrolyzing matrices that result in more porous particles. Kinetic annealing studies show that flavor molecules are entrapped quite efficiently even at high temperatures.

Decanoic Acids↗

Increased dopamine transporter density in the male rat brain following chronic nandrolone decanoate administration.

Adolescent males currently employ anabolic-androgenic steroids (AAS) to become intoxicated, besides the traditional desires of an improved physical appearance and enhanced sports performance. Several studies indicate that AAS affect the brain reward system. Recently chronic administration with nandrolone decanoate to male rats has been shown to increase the dopamine transporter (DAT) density in the striatum visualised in vivo by positron emission tomography. The present study aimed to investigate if the increased DAT density could be confirmed using in vitro autoradiography following a comparable regimen of nandrolone treatment. Specific binding of 50 pM [125I] RTI-55 in the presence of 1 microM citalopram was used to label DAT. Two weeks of nandrolone decanoate administration at the supra-therapeutic doses 1, 5 and 15 mg/kg per day increased DAT density in the caudate putamen at all three doses. In conclusion, this study confirms that chronic nandrolone administration increases dopamine transporter density in the CPU and therefore supports the theory that AAS affects the dopamine system in the male rat brain.

Anabolic Agents↗

The impact of chronic nandrolone decanoate administration on the NK1 receptor density in rat brain as determined by autoradiography.

Adult male Sprague-Dawley rats were treated with the anabolic androgenic steroid nandrolone decanoate (15 mg/kg day) or oil vehicle (sterile arachidis oleum) during 14 days. The effect on the densities of the neurokinin NK1 receptor in brain was examined with autoradiography. An overall tendency of attenuation of NK1 receptor density was observed after completed treatment with nandrolone decanoate. The density of the NK1 receptor was found to be significantly lower compared to control animals in the nucleus accumbens core (37% density reduction), in dentate gyrus (26%), in basolateral amygdaloid nucleus (23%), in ventromedial hypothalamic nucleus (36%), in dorsomedial hypothalamic nucleus (43%) and finally in the periaqueductal gray (PAG) (24%). In the cortex region, no structures exhibited any significant reduction of NK1 receptor density. This result provides additional support to the hypothesis that substance P and the NK1 receptor may be involved as important components that participate in mediating physiological responses including the adverse behaviors often associated with chronically administrated anabolic androgenic steroids in human.

Animals↗

Anabolic androgenic steroid nandrolone decanoate reduces hypothalamic proopiomelanocortin mRNA levels.

Supratherapeutical doses of anabolic androgenic steroids (AASs) have dramatic effects on metabolism in humans, and also inhibit feeding and reduce the rate of body weight gain in rats. In order to test the hypothesis that the AAS metabolic syndrome is accompanied by alterations in the central melanocortin system, we evaluated body weight, food intake and hypothalamic agouti-related protein (AgRP) and proopiomelanocortin (POMC) mRNA levels following administration of different doses of the anabolic androgenic steroid nandrolone decanoate. In order to distinguish changes induced by the steroid treatment per se from those resulting from the reduced food intake and growth rate, we also compared the effect of nandrolone decanoate on AgRP and POMC mRNA expression with both normally fed, and food restricted control groups. We here report that administration of nandrolone specifically reduces arcuate nucleus POMC mRNA levels while not affecting the expression level of AgRP. The effect on POMC expression was not observed in the food restricted controls, excluding the possibility that the observed effect was a mere response to the reduced food intake and body weight. These results raise the possibility that some of the metabolic and behavioural consequences of AAS abuse may be the result of alterations in the melanocortin system.

Agouti-Related Protein↗

The effects of 17 alpha-methyltestosterone, methandrostenolone, and nandrolone decanoate on the rat estrous cycle.

In a series of four separate experiments, the effects of anabolic-androgenic steroid (AAS) compounds on the estrous cycle of adult Long-Evans rats were examined. Sexual receptivity, vaginal cytology, and body weight were monitored throughout a 2-week baseline, AAS treatment, and recovery periods. In Experiments 1-3, subjects were administered 17 alpha-methyltestosterone, methandrostenolone, or nandrolone decanoate at doses selected to mimic the human abuse levels of each compound. In these studies, the highest doses of 17 alpha-methyltestosterone (7.5 mg/kg) and nandrolone decanoate (5.6 mg/kg) disrupted behavioral and vaginal cyclicity, whereas the highest dose of methandrostenolone (3.75 mg/kg) appeared to have slightly less robust effects. To compare effects on estrous cyclicity across AAS compounds, subjects in Experiment 4 received a single high dose (7.5 mg/kg) of each compound for 2 weeks. At this dose, all AAS compounds interfered with vaginal cyclicity, although effects on behavioral cyclicity and uterine weight were not uniform. Across all 4 experiments, AAS effects on body weight were minimal. The short-term administration of AAS compounds at levels commonly used by humans disrupts female neuroendocrine function in a dose-dependent manner.

Anabolic Agents↗