Current Drug Therapy - Volume 18, Issue 1, 2023

Depression is a chronic, devastating, and frequently occurring disease. Clinical studies have shown the association of depression with atrophy as well as degeneration of nerve cells and glial cells, which contribute to the size and function of specific brain regions that regulate the status of the mind, including depression. The currently available pharmacotherapies can be helpful in the treatment of psychosomatic disorders, including depression. Since these drugs display a very slow reaction and are required to be taken for a prolonged period, they often induce many side effects, which pose challenges in chemotherapy of the disease. The vascular endothelial growth factor A (VEGF) and the brainderived neurotrophic factor (BDNF) are known to play key roles in regulating the pathophysiology of depression. While searching for better options of treatment, rapid-acting antidepressants, such as the antagonist ketamine and N-methyl-D-aspartate NMDA receptor (NMDAR), are gaining more attention, which affects an array of signaling pathways. An evolutionary hypothesis suggests that the plasticity of neuronal routes is likely to be involved in the pathogenesis and hence the treatment of depression. It has been shown that due to the improper functioning of the neuronal system, adaptive plasticity can contribute to the pathogenesis of depression. Due to the use of medicines that promise choices for the treatment of depressive patients for dramatic improvement, there is an urgent need to develop novel tools about the mechanism of action of these rapid-acting antidepressants affecting the brain, particularly their interaction with the neuronal cell signaling pathways and their special effects on the neural circuits in the brain.

Background: Intranasal oxytocin can be used as a promising moiety for the treatment of sexual disorders. Objective: This study was carried out to systematically review the effect of intranasal oxytocin on sexual function in men and women. Methods: We systematically searched databases (e.g., Cochrane Central Register of Controlled Trials Library, MEDLINE, Web of Science, Scopus, ProQuest, Google Scholar and Persian databases). All types of published clinical trials comparing different doses of intranasal oxytocin sprays with placebo sprays were included in the study. The primary outcome was sexual function and secondary outcomes were endocrine and cardiovascular measures and also side effects. Results: A total of six studies were ultimately eligible for inclusion in the study. Though intranasal oxytocin improves various parameters of sexual function in men and women, according to the sexual response cycle, these changes are not statistically meaningful compared to the control group. Only one study revealed a meaningful impact on orgasm parameters and after orgasm, especially in men. In all studies, intranasal oxytocin administration has significantly and transiently increased plasma concentrations of oxytocin with no meaningful effect on other endocrine hormones. A study showed that the heartbeat is increased transiently during the arousal and orgasm stages, and such increase is meaningfully higher in men than in women. Conclusion: Intranasal oxytocin administration fails to meaningfully affect the classical parameters of sexual response, but it improves the orgasmic and post-orgasmic dimensions, especially in men. To evaluate the effects of intranasal oxytocin administrations, we need more long-term clinical trials.

Introduction: This study was devoted to the experimental study of the effect of Semax (Met-Glu-His-Phe-Pro-Gly-Pro) on the level of pro- and anti-inflammatory cytokines (IL-1β, IL-4, IL- 6, TNF-α, TGF-β1) in conditions of "social" stress. Aim of the Study: To study the effect of Semax on the level of pro- and anti-inflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) under conditions of “social” stress. Materials and Methods: White nonlinear rats (males, 6–8 months of age) were used as experimental animals. The animals were divided into groups: 1 – the control group (n=10); 2 – animals exposed to "social" stress (20 days) (n=10 aggressors/10 victims); 3 – rats exposed to "social" stress and receiving Semax intraperitoneally at a dose of 100 μg / kg / day (20 days) (n=10 aggressors/10 victims). Sensory contact was chosen as an experimental model of "social" stress. The level of cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) was determined by the method of enzyme-linked immunosorbent assay. Results: Currently, within the framework of the development of a direction to study the functioning of the unified cytokine network of the body, there is a need for a detailed analysis of changes in the production of individual cytokines during various pathophysiological reactions, including stressful effects. The experimental "social" stress is accompanied by an increase in the production of IL-1β, IL-6, TNF-α, TGF-β1, which allowed us to consider stress as the main inducer of the production of cytokines of the family of proinflammatory interleukins and various growth factors. It was previously thought that inflammation and the immune response are the only factors capable of causing the production of most cytokines. In recent years, scientific works have appeared in which stress occupies an important place among the inducers of cytokine production. This fact has been confirmed by our experiments. Experimental "social" stress is accompanied by changes in the production of IL-1β, IL-4, IL-6, TNF-α, TGF-β1, which allowed us to consider stress as the main inducer of the production of proinflammatory cytokines and growth factors. Conclusion: Evaluation of the effect of Semax on the level of cytokines under conditions of "social" stress showed that the effect of Semax is aimed at restoring the level of the studied cytokines in the group of stressed animals.

Background: This research aims to prepare a hydrogel of psoralen and capsaicin extract for topical application using various gelling agents like Carbopol 940, HPMC, Pluronic 127, and Pectin to minimize the side effect of synthetic drugs in treating psoriasis. Natural, synthetic, and semi-synthetic polymers were utilized for the treatment of psoriasis, and provide a number of benefits, including improved skin permeability, particularly for psoralen, and improved drug stability with improved therapeutic concentration gradients across the skin. Psoriasis is a T cell-mediated autoimmune disease affecting 2-3 % worldwide. Methods: FTIR and HPLC confirm the extract identification. pH, spreadability, homogeneity, extrudability, phase separation, viscosity, drug content, and stability analysis are all tested on all prepared hydrogels. The releases of psoralen from all prepared formulations are studied in phosphate buffer pH 6.8 using dialysis membranes at 37°C. Results: The net results conclude that hydrogels made using Carbopol-940 and HPMC (A1, A3, B2, B3) are the most superior and reliable formulations in terms of physicochemical parameters and in vitro permeation studies, out of which 1% carbopol 940 formulations (A3) showed maximum %CDR of 87.96 % much higher compared to other concentration used. Fitting data of the best formulations (A1, A3, B2, B3) obtained from in vitro drug permeation studies showed the release best fitted to the Korsmeyer-Peppas model as indicated by higher R² value. The optimum formulation (A3) has a higher R² value, which is then compared with the marketed formulation for the release of psoralen (in vitro), showing that %CDR of the A3 formulation (87.96%) is much higher than the %CDR of the marketed formulation (79.58%), due to the impact of capsaicin which acts as a penetration enhancer and therefore increases psoralen release from the hydrogel. Conclusion: As a result, the permeability issue with Psoralen for dermal drug administration has been overcome by using capsaicin as a permeability enhancer.

Background: Conventional drugs like metronidazole for periodontitis have shown several drawbacks. Based on in-vitro and acute toxicity studies on metronidazole-loaded n-trimethyl quaternary ammonium chitosan nanoparticles (NTMET NPs), animal studies were carried out to prove their enhanced activities against periodontitis. Objectives: This study aimed to assess the effect of nanoparticles through an intra-pocket drug delivery concerning body weight, food consumption, clinical signs, gingival index, tooth mobility, inflammatory changes in periodontal tissues, and serum analysis, leading to gingival damage, connective tissues, and alveolar bone resorption. Methods: A P. gingivalis and ligature-induced periodontitis model was used to evaluate the effect of the drug on rats. Results: Periodontitis was successfully induced by using P. gingivalis and ligature in rats. It reflected elevated gingival index, tooth mobility, inflammatory changes in tissues, IL-6, TNF- α, and IL -1β compared to the control group and NTMET NPs treated groups. It was also observed that the damage caused to gingival tissues and resorption of alveolar bone was improved by using NTMET NPs. Conclusion: Based on present findings, we can conclude that NTMET NPs at a dose of 1.8 and 3.6 mg/ml had significant action on periodontal tissues and were able to reverse the effect of P. gingivalis as well as gingival damage and tooth mobility in rats at an administered dose, which was comparable to the IC50 value of a drug. The findings of the current study provide preclinical scientific data to support their clinical use for periodontitis via an intra-pocket drug delivery route.

Background: Gastric cancer is a daunting global problem with unsatisfactory treatment. Due to the key role of Gastric Cancer Stem-like Cells (GCSCs) in all stages of gastric cancer and the failure of contemporary anticancer therapies, many research efforts are focusing on these treatmentresistant cells. Pantoprazole, as recently considered antitumor agent with well-documented effects on tumorigenesis inhibition, has seldom been investigated in GCSCs in previous studies. We aimed to study the influence of pantoprazole on cell proliferation, apoptosis, and the transcription of genes involved in the cell proliferation and apoptosis pathways. Materials and Methods: Herein, we isolated GCSCs from MKN-45 cell line, on a non-adherent surface and then evaluated the effect of pantoprazole on cell growth and apoptosis of GCSCs by means of MTT, DNA laddering and quantitative real-time RT-PCR techniques. Results: Our findings showed that treated cells with pantoprazole decreased cell proliferation and induced apoptosis. PCNA (Proliferating Cell Nuclear Antigen) and antiapoptotic Bcl2 genes were downregulated and Bax and CASP3 proapoptotic genes, as well as tumor suppressor p53 gene, were overexpressed. Conclusion: Our results revealed that pantoprazole induced apoptosis and declined tumor growth and support the idea that pantoprazole played as a promising breakthrough in gastric cancer therapy.

Background: Nanotechnology has been considered an auspicious approach over the last twenty years and numerous researchers are making efforts to extend its applications in pharmaceuticals. Recently, various nano-based drug delivery systems, such as nanoparticles, nanoemulgel, nanosuspension, and nanoemulsion, have been developed to deliver varieties of hydrophobics to target sites. Rosuvastatin is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase enzyme. The application of rosuvastatin is compromised because of its poor aqueous solubility and low oral bioavailability. Objective: This research work aimed to develop and characterize nanosuspension formulation for enhancement of the dissolution rate of rosuvastatin. Methods: Nanosuspension of rosuvastatin was prepared by using PVP K-30 and tween 80 as a stabiliser via the high-pressure homogenization method. The nanosuspension formulation was optimised by a factorial design to determine the effect of PVP K-30 (A), the concentration of tween 80 (B) and the number of the cycle (C) of high-pressure homogenizer on particle size (Y1), polydispersity index (Y2) and zeta potential (Y3) of the developed formulation. The optimised nanosuspension formulation of rosuvastatin was assessed for particle size, zeta potential, PDI, pH, % encapsulation efficiency of the drug, solubility study and comparative in vitro dissolution study. The optimised formulation passed the stability studies in terms of physical stability (sedimentation) for three months. Results: The optimised formulation resulted in 92.79 nm of particle size with a 0.201 polydispersity index. The nanosuspension of rosuvastatin showed higher dissolution rate as compared to the pure drug. Conclusion: This investigation demonstrated that nanosuspension preparation could be a promising approach for improvement of the dissolution rate of BCS II class drugs.