Current Reviews in Clinical and Experimental Pharmacology - Volume 19, Issue 2, 2024

Background: Parkinson's disease is the second most common neurological ailment. It is also known that it affects practically all other brain components, although only gradually. Animal models are mostly used to test the efficacy of treatment against a specific enzyme and aid in creating a new drug dose.Objective: The purpose of this review is to highlight in vivo Parkinson's disease screening approaches, as well as the mechanism of action of each drug involved in Parkinson's disease development, and discuss the limitations of each model. In addition, it also sheds light on Parkinson's disease genetic models.Methods: The data for the publication was gathered from databases, such as PubMed, Bentham Science, Elsevier, Springer Nature, Wiley, and Research Gate, after a thorough examination of diverse research findings linked to Parkinson's disease and its screening models.Results: Each chemical or drug has a unique mechanism for causing disease, whether through the production of reactive oxygen species or the blockage of the dopamine receptor. Almost every disease symptom, whether physical or behavioral, is covered by each of the constructed models' unique set of indicators and symptoms.Conclusion: Animal models are typically used to assess a medicine's activity against a specific enzyme and aid in the creation of a new drug dose. The process, restrictions, and mechanisms interfering with the screening, as well as the level of animal suffering, must all be thoroughly reviewed before any model for screening for Parkinson's disease can be implemented.

Chlorpheniramine Maleate (CPM), also known as chlorphenamine, is a potent alkylamine first-generation H1 antihistamine that has been used since the 1950s. CPM is a widely popular drug commonly used to treat allergic conditions, given its antihistamine properties. Although mainly used in over-the-counter treatment for cough and colds, various studies discuss a wide range of CPM's clinical uses, such as treating asthma, plasma cell gingivitis, chronic urticaria, and depression, among others. This antihistamine is usually taken orally; however, intravenous, intramuscular, and subcutaneous routes have been documented. Intranasal routes of this drug have recently been explored, especially due to its antiviral properties against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accordingly, given CPM's extensive medical and safety profile, the present review explores this versatile drug's current and potential clinical applications. Although it is widely used mainly for treating common colds and aforementioned allergic conditions, CPM can be used for other clinical indications. The repurposing of CPM for other clinical indications, such as COVID-19, needs to be further explored through more extensive studies.

Aging is a process characterized by accumulating degenerative changes resulting in the death of an organism. Aging is mediated by various pathways that are directly linked to the individual's lifespan and are shunted for many age-related diseases. Many strategies for alleviating age-related diseases have been studied, which can target cells and molecules. Modern drugs such as Metformin, Rapamycin, and other drugs are used to reduce the effects of age-related diseases. Despite their beneficial activity, they possess some side effects which can limit their applications, mainly in older adults. Natural phytochemicals which have anti-aging activities have been studied by many researchers from a broader aspect and suggested that plant-based compounds can be a possible, direct, and practical way to treat age-related diseases which has enormous anti-aging activity. Also, studies indicated that the synergistic action of phytochemicals might enhance the biological effect rather than the individual or summative effects of natural compounds. Curcumin has an antioxidant property and is an effective scavenger of reactive oxygen species. Curcumin also has a beneficial role in many age-related diseases like diabetes, cardiovascular disease, neurological disorder, and cancer. Aged garlic extracts are also another bioactive component that has high antioxidant properties. Many studies demonstrated aged garlic extract, which has high antioxidant properties, could play a significant role in anti-aging and age-related diseases. The synergistic effect of these compounds can decrease the requirement of doses of a single drug, thus reducing its side effects caused by increased concentration of the single drug.

The 5-HT syndrome in rats is composed of head weaving, body shaking, forepaw treading, flat body posture, hindlimb abduction, and Straub tail. The importance of the brainstem and spinal cord for the syndrome is underlined by findings of 5,7-dihydroxytryptamine (5,7-DHT)-induced denervation supersensitivity in response to 5-HT-stimulant drugs. For head weaving and Straub tail, supersensitivity occurred when the neurotoxin was injected into the cisterna magna or spinal cord, for forepaw treading in cisterna magna, and for hindlimb abduction in the spinal cord. Although 5,7- DHT-related body shaking increased in the spinal cord, the sign decreased when injected into the striatum, indicating the modulatory influence of the basal ganglia. Further details on body shaking are provided by its reduced response to harmaline after 5-HT depletion caused by intraventricular 5,7-DHT, electrolytic lesions of the medial or dorsal raphe, and lesions of the inferior olive caused by systemic injection of 3-acetylpyridine along with those found in Agtpbp1^pcd or nr cerebellar mouse mutants. Yet the influence of the climbing fiber pathway on other signs of the 5-HT syndrome remains to be determined.

Background: Recurrent glioblastoma multiforme (rGBM) has a grim prognosis, with current therapies offering no survival benefit. Several combination therapies involving anti-VEGF agents have been studied with mixed results.Methods: A systematic search was performed using five electronic databases: PubMed, Scopus, ISI, Embase, and the Cochrane Library, without language limitations. The primary outcome of interest was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response ratio (ORR), and grade 137;¥ 3 adverse events. Estimates for PFS and OS were calculated as random effects hazard ratio (HR) with 95% confidence intervals (CIs) using the generic inverse variance method. Estimates for ORR and grade 137;¥ 3 adverse events were calculated using a random-effects risk ratio (RR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method.Results: Thirteen studies met the inclusion criteria and a total of 1994 patients were included in the analysis. There was no statistically significant improvement in PFS (HR 0.84; 95% CI (0.68, 1.03); I²=81%), OS (HR 0.99; 95% CI (0.88, 1.12); I²=0%), and ORR (RR 1.36; 95% CI (0.96, 1.92); I²=61%) in the combination therapy group when compared to the control group. Significantly higher grade 137;¥ 3 adverse events (RR 1.30; 95% CI (1.14, 1.48); I²=47%) were seen in the combination therapy when compared to the control group.Conclusion: Our analysis showed that the use of combination therapy with anti-VEGF agents did not offer any benefit in PFS, OS, or ORR. In contrast, it had significantly higher grade 3-5 adverse events. Further studies are needed to identify effective therapies in rGBM that can improve survival.

Objective: Helicobacter pylori infects at least 50% of the world's human population. The current study aimed to assess and compare the efficacy of triple versus quadruple therapy.Methods: Randomized clinical trials (RCTs) consisting of triple and quadruple therapy were identified through electronic and manual searches in the national and international online databases (IsI, Magiran, Embase, PubMed, and Scopus). The random-effects model was applied to pool analysis. Funnel plots and the Egger test were used to examine publication bias.Results: After a detailed review of the selected articles, 80 RCTs were included in the meta-analysis; it was based on using triple and quadruple therapy as the first and second-line treatment. The results showed that quadruple therapy in the first-line treatment had a higher eradication rate than triple therapy. Overall, the eradication rate with triple therapy was 74% (95% CI, 71%-77%) for intention-totreat (ITT) analysis and 80% (95% CI, 77%-82%) for per-protocol (PP) analysis. Generally, the eradication rate with quadruple therapy was 82% (95% CI, 78.0%-86.0%) for ITT analysis and 85% (95% CI, 82.0%-89.0%) for PP analysis. The analysis also revealed that quadruple therapy was more effective for 7 or 10 days.Conclusion: The current study results demonstrated that quadruple therapy has better effectiveness than triple therapy as the first-line treatment; however, in the second-line treatment, the effectiveness of quadruple and triple regimens is almost similar. The effectiveness of quadruple therapy in the Asian population was found to be slightly higher than that of triple therapy, while this difference was considerably higher in the European population.

Objectives: Intrapleural thrombolytics have been trialed for facilitating pleural fluid drainage in patients with complicated parapneumonic effusion. The present study is a network metaanalysis of randomized clinical trials (RCTs) that have evaluated these thrombolytics.Methods: Electronic databases (Medline, Cochrane CENTRAL, and Google Scholar) were searched for appropriate RCTs evaluating the therapeutic effect of thrombolytics in patients with complicated parapneumonic effusion. Mortality, the proportion of patients referred for surgical intervention, and serious adverse events were the outcome measures. Random-effects model was used for generating direct and mixed treatment comparison pooled estimates. Grading of the evidence for key comparisons was carried out. Odds ratio with 95% confidence intervals was used to represent the pooled estimates.Results: Seventy-six studies were retrieved with the search strategy, of which 16 were included. No significant differences were observed in mortality. Compared to normal saline, significantly less proportion of patients was referred for surgical intervention with streptokinase (0.4, 0.2 to 0.8), urokinase (0.4, 0.2 to 0.8), alteplase (0.3, 0.1 to 0.7), and alteplase + DNase (0.2, 0.1 to 0.7). DNase alone increased the risk of referral to surgical intervention (3.4, 1.5 to 7.6). Only streptokinase was observed with an increased risk of serious adverse events compared to normal saline (2.8, 1.1 to 7.1) and alteplase (6.7, 1.1 to 39.9). Moderate quality of evidence was observed for streptokinase with normal saline for the proportion of patients referred for surgical intervention, while either low or very low quality strength was observed for all other comparisons.Conclusion: Streptokinase, urokinase, alteplase, and alteplase + DNase were observed in patients referred for surgical interventions when used intrapleural in patients with parapneumonic effusion. Alteplase + DNase is likely to outperform others as it was observed with the least risk of patients referred for surgical interventions. Until additional data emerges that changes the pooled estimates, thrombolytics other than streptokinase are preferred due to the increased risk of serious adverse events.