Raloxifene 60mg tablets

Recognizing the robust sex differences in schizophrenia prevalence, the selective estrogen receptor modulator (SERM) raloxifene is a likely candidate for augmentation therapy in this disorder. Therefore, a systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Randomized controlled trials investigating the effect of raloxifene in schizophrenia spectrum disorders were included in the quantitative analyses. Outcome measures were psychotic symptom severity, depression, and cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random-effects model was used to compute overall weighted effect sizes in Hedges' g. Nine studies were included, investigating 561 patients with a schizophrenia spectrum disorder. Raloxifene was superior to placebo in improving total symptom severity (N = 482; Hedge's g = .57, p = 0.009), as well as positive (N = 561; Hedge's g = 0.32, p = 0.02), negative (N = 561; Hedge's g = 0.40, p = 0.02), and general (N = 526; Hedge's g = 0.46, p = 0.01) subscales, as measured by the Positive and Negative Syndrome Scale. No significant effects were found for comorbid depression and cognitive functioning. Altogether, these results confirm the potential of raloxifene augmentation in the treatment of schizophrenia.

Abstract licence: CC BY

BACKGROUND AND HYPOTHESIS: Several studies suggest that raloxifene, a selective estrogen receptor modulator, improves symptoms and cognition in post-menopausal women with Schizophrenia-Spectrum Disorders (SSD). We aimed to assess the effects of adjunctive raloxifene in women and men with SSD. STUDY DESIGN: This parallel, randomized, double-blind, placebo-controlled trial included adult SSD patients across the Netherlands and Belgium. Participants were stratified by age, sex, and global functioning and randomly assigned 1:1 to 12-week add-on raloxifene or placebo. Primary outcomes were symptom severity at 6, 12, and 38 weeks and cognition at 12 and 38 weeks, as measured with the Positive and Negative Syndrome Scale and the Brief Assessment of Cognition in Schizophrenia, respectively. Intention-to-treat analyses were performed using linear mixed-effect models. STUDY RESULTS: We assessed 261 patients for eligibility, of which 102 (28% female) were assigned to raloxifene (n = 52) or placebo (n = 48). Although we found no main effect of raloxifene, secondary sex-specific analysis showed that in women, raloxifene had beneficial effects on negative symptoms at week 6 (LSM -2.92; adjusted P = 0.020) and week 12 (LSM -3.12; adjusted P = 0.030), and on working memory at week 38 (LSM 0.73; adjusted P = 0.040), while having negative effects on working memory at week 38 in men (LSM -0.53; adjusted P = 0.026). The number of adverse events was similar between groups. CONCLUSIONS: Our results do not support the use of raloxifene in patients with SSD in general, but suggest female-specific beneficial effects of raloxifene on negative symptoms and working memory. Our findings encourage further research on sex-specific pharmacotherapeutic treatment.

Abstract licence: CC BY-NC

The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 3(2) factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and -12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX.

Abstract licence: CC BY-NC-ND

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates strategies to identify prophylactic and therapeutic drug candidates to enter rapid clinical development. This is particularly true, given the uncertainty about the endurance of the immune memory induced by both previous infections or vaccines, and given the fact that the eradication of SARS-CoV-2 might be challenging to reach, given the attack rate of the virus, which would require unusually high protection by a vaccine. Here, we show how raloxifene, a selective estrogen receptor modulator with anti-inflammatory and antiviral properties, emerges as an attractive candidate entering clinical trials to test its efficacy in early-stage treatment COVID-19 patients.

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Recent studies have shown that the selective estrogen receptor modulator (SERM) raloxifene had pronounced protective effects against progressing brain damage after traumatic brain injury (TBI) in mice. These studies, indicating beneficial effects of raloxifene for brain health, prompted the study of the history and present state of knowledge of this topic. It appears that, apart from raloxifene, to date, four nonrelated compounds have shown comparable beneficial effects-fucoidan, pifithrin, SMM-189 (5-dihydroxy-phenyl]-phenyl-methanone), and translocator protein (TSPO) ligands. Raloxifene, however, is ahead of the field, as for more than two decades it has been used in medical practice for various chronic ailments in humans. Thus, apart from different types of animal and cell culture studies, it has also been assessed in various human clinical trials, including assaying its effects on mild cognitive impairments. Regarding cell types, raloxifene protects neurons from cell death, prevents glial activation, ameliorates myelin damage, and maintains health of endothelial cells. At whole central nervous system (CNS) levels, raloxifene ameliorated mild cognitive impairments, as seen in clinical trials, and showed beneficial effects in animal models of Parkinson's disease. Moreover, with stroke and TBI in animal models, raloxifene showed curative effects. Furthermore, raloxifene showed healing effects regarding multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) in cell culture. The adverse biological signals typical of these conditions relate to neuronal activity, neurotransmitters and their receptors, plasticity, inflammation, oxidative stress, nitric oxide, calcium homeostasis, cell death, behavioral impairments, etc. Raloxifene favorably modulates these signals toward cell health-on the one hand, by modulating gene expression of the relevant proteins, for example by way of its binding to the cell nuclear estrogen receptors ERα and ERβ (genomic effects) and, on the other hand (nongenomic effects) by modulation of mitochondrial activity, reduction of oxidative stress and programmed cell death, maintaining metabolic balance, degradation of Abeta, and modulation of intracellular cholesterol levels. More specifically regarding Alzheimer's disease, raloxifene may not cure diagnosed Alzheimer's disease. However, the onset of Alzheimer's disease may be delayed or arrested by raloxifene's capability to attenuate mild cognitive impairment. Mild cognitive impairment is a condition that may precede diagnosis of Alzheimer's disease. In this review, relatively new insights are addressed regarding the notion that Alzheimer's disease can be caused by bacterial (as well as viral) infections, together with the most recent findings that raloxifene can counteract infections of at least some bacterial and viral strains. Thus, here, an overview of potential treatments of neurodegenerative disease by raloxifene is presented, and attention is paid to subcellular molecular biological pathways that may be involved.

Abstract licence: CC BY