Current Reviews in Clinical and Experimental Pharmacology - Volume 21, Issue 1, 2026
Volume 21, Issue 1, 2026
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Neurobiological Mechanisms of Ketamine Use, its Addiction, and Withdrawal: A Mini Review
More LessKetamine, a substance used for anesthesia and known for inducing dissociation, can lead to addiction and the development of severe withdrawal symptoms. Ketamine alters brain networks before affecting somesthetic sensation. Ketamine abuse was especially prevalent in East and Southeast Asia, and its popularity has continued to expand globally in recent decades. Ketamine is gaining popularity in the public and private sectors as a cheaper off-label depression treatment. Unfortunately, ketamine may cause side effects, such as heart and blood vessel instability, respiratory depression, liver injury, hallucinations, etc. The pain-relieving and mental effects of ketamine might induce reliance; thus, it should be used cautiously. This review highlights the neurobiological processes underpinnings of ketamine's addictive potential, withdrawal, and its effects on brain networks like the prefrontal cortex, hippocampus, and mesolimbic pathway, which play vital roles in decision-making, memory, and reward processing. In addition, the involvement of neurotransmitter systems, specifically glutamate and dopamine, in mediating the addictive properties of ketamine and the neuroadaptive changes that occurred during withdrawal are also discussed. It also explains that low-dose ketamine can alter the secretion of stress hormone cortisol and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, possibly attributed to the current repurposing study of ketamine as a fast-acting antidepressant. Understanding these pathways is essential for developing effective ketamine addiction treatments, managing withdrawal symptoms, and possibly reversing brain changes for the betterment of human health and psychological well-being.
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Breaking the Mold: Advances and Hurdles in Antifungal Resistance Management for Dermatophytes
More LessExamining antifungal resistance in dermatophytes is crucial in infectious diseases, dermatology, and clinical microbiology. The increasing occurrence of resistant infections and their influence on the effectiveness of therapy seem overwhelming. This study examines the present condition of antifungal resistance in dermatophytes, highlighting the need for ongoing and up-to-date research. Fungal diseases constantly change, and fungi have developed new resistance mechanisms. Here, we analyze the historical context of research on antifungal resistance, examining the variables that contribute to the development of resistance, such as the growing use of antifungals in clinical and agricultural contexts. We also explore the consequences of resistance to antifungal agents in clinical practice and public health. The review emphasizes the significance of new diagnostic technologies, like next-generation sequencing, in comprehending resistance mechanisms. It also underscores the crucial role of international collaboration in tackling this worldwide health concern. In conclusion, the paper emphasizes the need for continuous research to adjust to the evolving epidemiology of dermatophyte infections, create efficient treatment approaches, and guide public health interventions. This will ensure that the management of antifungal resistance is grounded in the most up-to-date scientific knowledge and optimal methods.
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The Gut Connection: A Narrative Review on the In-depth Analysis of Gut Microbiota and Metabolites in Depression
More LessDepression is a prevalent mood disorder with significant public health implications. Despite extensive research, its precise causes remain inadequately understood. Recently, interest has surged in the role of the gut microbiome and its metabolites in the pathophysiology of depression. This review aims to provide a comprehensive overview of the relationship between gut microbiota, its metabolites, and depression while exploring potential mechanisms influencing the efficacy of antidepressant medications. A narrative review methodology was employed, synthesizing recent studies utilizing a multi-omics approach. We examined alterations in gut microbiome composition and metabolite production in individuals diagnosed with depression, discussing the technical tools and methods commonly applied in this research area. The findings indicate that individuals with depression show significant alterations in gut microbiome composition, notably an imbalance in Firmicutes, Bacteroidetes, and Actinobacteria. Changes in metabolite production, including short-chain fatty acids, tryptophan, and bile acids, were also observed. Moreover, the review highlights that antidepressant medications may exert their therapeutic effects by modulating gut microbiota and its metabolites. This review emphasizes the intricate interplay between gut microbiota, its metabolites, and depression, revealing critical insights into the mechanisms underlying antidepressant efficacy. We recommend that future research focus on elucidating these interactions to develop innovative therapeutic strategies, potentially transforming the management of depression through microbiota-targeted approaches.
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Fisetin, a Promising Anti-Cancer Flavonoid: A Brief Review of Its Biological Effects and Molecular Mechanisms in Lung Cancer Prevention and Therapy
More LessIntroductionExperimental evidence has demonstrated that compounds of natural origin possess adjuvant anti-cancer properties, and their combination with anti-cancer drugs has the potential to reduce drug resistance in cancer treatment exhibiting chemoprotective effects.
MethodsFisetin (FIS), a flavonoid-structured polyphenolic compound found in various vegetables and fruits, is used as a yellow/ochre coloring agent and shows diverse pharmacological and biological effects. FIS can modulate various signaling pathways in relation to oxidative stress, inflammation, cell proliferation, metastasis, and angiogenesis. Thus, FIS is proposed to be a beneficial agent for preventing and treating numerous human malignancies. Awareness of natural compound action mechanisms paves the way for scientific communities, healthcare organizations, and the pharmaceutical industry to develop and introduce new drugs to treat diseases. In this paper, the general properties of FIS were highlighted first, and later, using the Scopus database, all related scientific literature regarding the studies that investigated the effects of FIS on lung cancer was collected.
ResultsThe critical points were extracted from the research works, and possible effects and molecular mechanisms of FIS on cancer cells were reviewed, and a comprehensive discussion about the roles of this phytochemical on different signaling pathways that were very crucial in lung cancer cells was provided.
ConclusionFinally, the current challenges and future perspectives of lung cancer prevention and therapy approaches using FIS were addressed.
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Genetic Determinants of Statin-induced Myopathy: A Network Meta-analysis of Observational Studies
More LessAuthors: Kannan Sridharan and Gowri SivaramakrishnanIntroductionStatin-induced myopathy (SIM) is a prevalent adverse event impacting treatment adherence. Despite extensive exploration of single nucleotide polymorphisms (SNPs), conflicting evidence obscures their role in SIM incidence, prompting this network meta-analysis.
MethodsObservational studies meeting eligibility criteria (patients on any statin with reported SNPs and SIM details) were systematically reviewed. Severe SIM was defined as creatine kinase elevations exceeding 10 times the upper limit of normal. Mixed treatment comparison pooled estimates were generated from direct and indirect pooled estimates, represented by odds ratios (OR) with 95% confidence intervals (CI), and validated via bootstrap analysis.
ResultsThirty-four studies (26,152 participants) examining genotypes spanning drug transporters, metabolizing enzymes, reactive oxygen species production, and myopathy-related genes were analyzed. Significant associations were observed with drug transporters (OR: 1.4; 95% CI: 1.04, 1.5). Notably, solute carrier organic anion transporter 1B1 (SLCO1B1) (rs4149056) exhibited a moderate association with SIM (OR: 2.1; 95% CI: 1.7, 2.6), validated by bootstrap analysis (OR: 2.1; 95% CI: 1.7, 2.8). Similar associations were found for severe SIM with SLCO1B1 (rs4149056) (OR: 3.8; 95% CI: 1.4, 10.4) and ATP Binding Cassette Subfamily B Member 1 (ABCB1) (rs2373588) (OR: 2.8; 95% CI: 1.4, 5.4). Intraclass differences in genetic predictor risks were noted among statins.
ConclusionOur meta-analysis underscores the significant association of SLCO1B1 with SIM, supporting its clinical utility. Further research is warranted to clarify additional genetic predictors. These findings endorse current guidelines advocating for SLCO1B1 genotyping in statin therapy decisions.
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