New Potential Beta-3 Adrenergic Agonists with Beta- Phenylethylamine Structure, Synthesized for the Treatment of Dyslipidemia and Obesity

Beta-3 adrenergic receptors have important physiological implications, being expressed in many places in the body, including brown adipose tissue. Of the effects studied in preclinical research on lipid metabolism attributable to stimulation of these receptors, we can mention the increased thermogenesis and metabolic rate in the brown adipose tissue, reduction of body weight in obese diabetic rats, lowering of intra-abdominal and subepithelial fat in nonobese and nondiabetic rats, decrease of triglyceride, and increase of HDL cholesterol levels. Carbohydrate metabolism is also changed by beta-3 adrenergic agonists, the most prevalent effects being blood glucose lowering in diabetic rats, increasing insulin secretion of the pancreas, or increasing glucose tolerance. Metabolic effects of 13 newly synthesized compounds of beta-phenylethylamine structure and reference BRL 37344 were investigated in order to identify a potential affinity for beta-3 adrenergic receptors. The antidiabetic and hypolipemiant effects were investigated on a rat model of alloxan-induced diabetes. The results demonstrated that new beta-phenylethylamine derivatives produced marked biological activity over lipid profile. All compounds have markedly decreased the values of total cholesterol, LDL cholesterol, and triglycerides and also have increased the values of antiatherogenic HDL cholesterol. The effects were significantly more intense than the reference substance BRL 37344

Behavioural and molecular study of the effects of rosuvastatin on acquisition and retention of spatial memory impaired by H-89 in rats

There is controversy on the effect of statins on cognitive functions such as spatial memory. In the present study, effect of ten- day oral gavage of rosuvastatin (Ros, 20 mg/kg) on spatial learning and spatial memory retention impaired by H-89, was investigated in male rats. This study was comprised of two sets of experiments each including the following 3 groups (n = 8): Control group treated with DMSO; H-89 group received bilateral intra-hippocampal H-89 (10 μM/side, in DMSO) and Ros- H-89 group orally treated with Ros (20 mg/kg) and H-89 (similar to the H-89 group). For spatial learning (acquisition phase) assessment, from day 7 of Ros gavage, rats were trained in the Morris water maze (MWM) for four days (one block of 4 stages each day) and received daily H-89, 30 min after Ros gavage. On day 11, the probe test was performed. Also, to assess spatial memory retention, from day 7 to 10 of Ros gavage, rats were trained in MWM but received H-89 on day 10 only. On day 12, the probe test was performed. Besides, CREB and p-CREB protein expression was assessed in hippocampal samples and oxidative stress status was assessed in serum samples. We observed that H-89 led to a clear impairment of the spatial learning and spatial memory recall, increased levels of lipid peroxidation and downregulated CREB and p-CREB proteins, compared to the control group. However, Ros prevented H-89-induced deleterious consequences which might be probably in part due to its ameliorative effects on lipid peroxidation index and CREB and p-CREB expression

COVID-19-Current Therapeutical Approaches and Future Perspectives

The ongoing pandemic of coronavirus disease (COVID-19) stimulated an unprecedented international collaborative effort for rapid diagnosis, epidemiologic surveillance, clinical management, prevention, and treatment. This review focuses on the current and new therapeutical approaches, summarizing the viral structure and life cycle, with an emphasis on the specific steps that can be interfered by antivirals: (a) inhibition of viral entry with anti-spike monoclonal antibodies; (b) inhibition of the RNA genome replication with nucleosidic analogs blocking the viral RNA polymerase; (c) inhibition of the main viral protease (Mpro), which directs the formation of the nonstructural proteins. An overview of the immunomodulatory drugs currently used for severe COVID-19 treatment and future therapeutical options are also discussed