Current pharmaceutical design最新文献

{"title":"The Synergistic Role of Phenolic Compounds in Docetaxel Chemoresistance in Prostate Cancer: A Systematic Review and Meta-Analysis.","authors":"Ramanjireddy Tatiparthi, Alaa A A Aljabali, Yachana Mishra, Vijay Mishra","doi":"10.2174/0113816128479433260709091532","DOIUrl":"https://doi.org/10.2174/0113816128479433260709091532","url":null,"abstract":"<p><strong>Background: </strong>Docetaxel (DTX) is the first-line treatment for androgen-deprived prostate cancer. Its long-term therapeutic stress provokes therapeutic resistance via compensatory pathways. Several phenolic compounds have demonstrated synergistic effects on DTX chemosensitization; these quantitative measures have not yet been addressed. This study aims to identify the best adjunct phenolic compound that demonstrates synergy with DTX chemosensitization.</p><p><strong>Methods: </strong>A comprehensive search was conducted in accordance with the PRISMA 2020 guidelines. Independent authors searched six databases for in vitro or in vivo studies until September 2025. The outcomes measured included the mean combination index (CoI), the fold-change in IC50, apoptosis, proliferation, migration, and tumor volume inhibition. Their results were pooled in a random-effects model to estimate the standard mean difference relative to control studies. The risk of bias was assessed using SciRAP for in vitro studies and ARRIVE 2.0 for in vivo xenograft studies.</p><p><strong>Results: </strong>Twelve preclinical studies met the eligibility criteria. The phenolic compounds with synergistic effects in combination with DTX were Curcumin (CCM), Quercetin (QUR), Caffeic Acid Phenethyl Ester (CAPE), and Honokiol (HKI). The meta-analysis study revealed significant apoptosis induction (SMD = 1.83; 95% CI: 0.92-2.75), IC50 values (SMD=2.00; 95% CI:0.88, 4.52), and tumor growth reduction (SMD = -3.15; 95% CI: -4.62 -1.68). The mechanisms of resistance reversal pathways identified included NF-κB, PI3K/AKT, and STAT3 inhibition, as well as blocking, reversing, and downregulating the P-glycoprotein efflux pump to overcome DTX resistance.</p><p><strong>Discussion: </strong>Among the tested compounds, CCM and CAPE demonstrated the highest synergistic potency, as indicated by combination index values and fold-change in IC50. QUR showed superior anti-proliferative activity in DTX-resistant cell lines, and HKI achieved the most significant in vivo tumor regression (SMD = -7.56). RES showed predominantly additive activity and is included for comparative analysis. However, the combination index was the lowest for CCM, demonstrating the highest synergistic activity among the methods and models employed. Curcuminoids, such as calebin A, tetrahydrocurcumin, and hispolon, are recommended for further in vitro studies. The risk of bias assessment indicated high methodological reliability among the in vitro studies and moderate quality in the animal studies.</p><p><strong>Conclusion: </strong>Overall, phenolic compounds were found to be credible adjuncts to the DTX combination. Among them, CCM was found to be the most synergistic agent across all tested methods. However, further clinical studies are warranted in prostate cancer patients.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of Drug-Drug Interactions and Initial Dosage Administration of Oxcarbazepine in Elderly Patients with Epilepsy.","authors":"Hai-Bo Zhang, Su-Mei He, Jie Wang, Dong-Dong Wang, Zheng-Quan Yu","doi":"10.2174/0113816128477482260723062011","DOIUrl":"https://doi.org/10.2174/0113816128477482260723062011","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate whether there were potential drug-drug interactions (DDI) of oxcarbazepine in elderly patients with epilepsy during clinical combination therapy and explore the optimal initial dosage regimen of oxcarbazepine for elderly patients with epilepsy.</p><p><strong>Methods: </strong>The effectiveness of oxcarbazepine was mainly determined by measuring the concentrations of its active metabolite, 10-hydroxycarbazepine (MHD). The study developed an MHD population pharmacokinetic (PPK) model for elderly patients with epilepsy using nonlinear mixed-effect modelling (NONMEM).</p><p><strong>Results: </strong>It was found that no combined medications significantly affected the pharmacokinetic processes of MHD. Further, we simulated and recommended the optimal initial dosages of oxcarbazepine suitable for elderly patients with epilepsy. Dosages of 20, 15, 10, and 5 mg/kg oxcarbazepine were recommended for elderly patients with epilepsy who weighed 40-46 kg, 46-55 kg, 55-76 kg, and 76-100 kg, respectively. At the same time, in accordance with the above administration plan, the probabilities of achieving the target concentrations of the oxcarbazepine active metabolite in elderly patients with epilepsy were 99.0-99.4%, 99.0-99.5%, 98.7-99.6%, and 98.7-99.7%, respectively.</p><p><strong>Discussion: </strong>The study explored potential DDIs and the initial dosage administration of oxcarbazepine in elderly patients with epilepsy for the first time. Combined medications did not cause DDI when used by elderly patients with epilepsy for treatment, demonstrating the high safety of oxcarbazepine in the treatment of elderly patients with epilepsy.</p><p><strong>Conclusion: </strong>This study recommended the initial dosages of oxcarbazepine for elderly patients with epilepsy. To achieve the same therapeutic concentration ranges, the dosages for elderly patients with epilepsy may need to be reduced.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Review on the Development and Challenges of Osmotically Activated Drug Delivery Systems.","authors":"Mounika Gadila, Bhavya Mallareddygari, Saipriya Naikoti, Manasa Voggu, Bappaditya Chatterjee","doi":"10.2174/0113816128460178260730113341","DOIUrl":"https://doi.org/10.2174/0113816128460178260730113341","url":null,"abstract":"<p><p>Osmotically activated drug delivery systems provide zero-order drug release kinetics that are independent of gastrointestinal pH. However, they may be partially affected by food effects and gastrointestinal motility, similar to other sustained-release oral drug delivery systems. Such delivery systems have the advantages of improved patient compliance, reduced dosing frequency, and predictable in vitro-in vivo correlation. However, several issues restrict its translation from the lab to clinical usage. The challenges associated with the osmotically activated delivery systems include formulation and manufacturing challenges such as drug solubility, manufacturing complexities, stability issues due to moisture sensitivity, limited drug loading in implants, orifice fabrication, etc. Other translational challenges include patient restrictions related to tablet size, variable physiological dependence, and high production costs. This review has provided an outline of different types of osmotic pumps with emphasis on the challenges and the possible approaches to overcome them. Additionally, commercially available products and clinical trial outcomes have been discussed, indicating their therapeutic benefits in several diseases such as Attention Deficit Hyperactivity Disorder (ADHD), schizophrenia, cancer, etc.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin Mitigates Hemodynamic, Autonomic, Oxidative, and Inflammatory Dysregulation in L-NAME-Induced Preeclampsia.","authors":"Sher Afghan, Huma Quasimi, Md Iqbal Alam, Sheema Wazib, Yashesvi Ambardar, Shikha Gautam","doi":"10.2174/0113816128463168260724045843","DOIUrl":"https://doi.org/10.2174/0113816128463168260724045843","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiovascular complications in preeclampsia are challenging and have been known to increase fetal and maternal morbidity and mortality. The objective of this study is to determine how metformin affects BP, HR, ECG, oxidative stress, and inflammatory markers in a preeclampsia-like rat model induced by L-NAME in female albino Wistar rats.</p><p><strong>Methods: </strong>Pregnant rats were randomly divided into four experimental groups: Group I (PC) the pregnant control, received normal saline: Group II (PEC) was treated intraperitoneally with 125 mg/kg/day of L-NAME from GD 13 -21: Group III (MetC) received 400 mg/kg/day Metformin orally from GD 13-GD21; and Group IV(T) was treated with L-NAME (125 mg/kg/day) and Met (400mg/kg/day) from \"GD 13- 21\". \"ECG, hemodynamic, sand Baroreflex Sensitivity (BRS)\" values were monitored at Gestational Day 21. Furthermore, cardiac tissue homogenates were evaluated for oxidative stress markers (MDA, GSH, and SOD) as well as inflammatory cytokines (TNF-α and IL-6).</p><p><strong>Results: </strong>The results showed that the Preeclampsia-like rat model significantly altered the ECG, resulting in increased duration of QRS and TpTe intervals and prolonged RR and QTc intervals. Metformin prevented these changes in rats. In addition, L-NAME decreased heart rate and increased systolic, diastolic, and mean arterial pressures; these effects were reversed by metformin. Elevated MDA indicated oxidative stress in cardiac tissue homogenates. These alterations were largely reversed by metformin, indicating that it had anti-inflammatory and antioxidant effects.</p><p><strong>Discussion: </strong>A preeclampsia-like rat model was induced using L-NAME in rats during pregnancy, resulting in hypertension, ECG abnormalities, oxidative stress, and inflammation. Metformin possesses strong cardioprotective, antioxidant, and anti-inflammatory effects, normalizing blood pressure and ECG intervals, reducing urinary protein levels, decreasing MDA levels, and increasing GSH and SOD contents, while also inhibiting the release of TNF-α and IL-6.</p><p><strong>Conclusion: </strong>In this study, we observed that metformin attenuated hypertension, ECG changes, oxidative stress, and inflammation in a preeclampsia-like rat model. Moreover, metformin enhanced baroreflex sensitivity, leading to partial recovery of autonomic cardiovascular regulation along with improved glycemic control. These results indicate that metformin could be a potential therapeutic intervention for the cardiovascular consequences of preeclampsia.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing Intelligent Antibacterial Systems via Piezoelectric Catalysis: Mechanisms and Pharmaceutical Perspectives.","authors":"Manaf AlMatar, Imen Ben Abdelmalek, Raja Lakhal","doi":"10.2174/0113816128481537260728073043","DOIUrl":"https://doi.org/10.2174/0113816128481537260728073043","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) is a critical global health challenge driven primarily by the inappropriate and excessive use of antibiotics in veterinary and human medicine. The misuse of antibiotics has contributed to the emergence of resistant bacteria, a situation increasingly described as a \"silent pandemic\" and projected to cause a substantial global mortality burden by 2050. AMR threatens both human and animal health by diminishing the effectiveness of antimicrobial therapy and making infections increasingly difficult to treat. Bacteria can evade conventional antibiotics through several mechanisms, including enzymatic degradation, active efflux, target-site mutations, reduced membrane permeability, and biofilm formation. Recently, piezoelectric catalysis has gained attention as an alternative antibacterial strategy based on the generation of Reactive Oxygen Species (ROS) under localized electric fields induced by mechanical stimulation, resulting in bacterial cell damage regardless of the resistance phenotype. This review outlines the mechanisms and evolution of AMR and highlights the antibacterial potential of piezoelectric materials grouped by family, including metal oxides such as ZnO and BaTiO3, transition metal sulfides such as MoS2, heterojunctions such as KNbO3/MoS2, and organic polymers such as PVDF. Current evidence indicates that ultrasonic activation of BaTiO3- and ZnO-containing materials can eliminate more than 97% of multidrug-resistant microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli, through ROS-mediated oxidative stress and electroporation. Despite promising findings from in vitro and preclinical studies, several translational barriers remain, including potential cytotoxicity associated with excessive ROS generation, challenges in scalable nanomaterial fabrication, and regulatory approval requirements. Future applications may include implant coatings, self-sterilizing wound dressings, and other infection-control technologies. Overall, this review provides a framework for future research by discussing the molecular basis, material-design strategies, and clinical translation challenges of piezocatalytic antibacterial systems in the fight against AMR.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Advances of AI in Drug Development.","authors":"Nitin Srivastava, Abhishek Srivastava, Devdutt Chaturvedi, Braj Kishore Rathour, Krishna Srivastava","doi":"10.2174/0113816128463896260727092221","DOIUrl":"https://doi.org/10.2174/0113816128463896260727092221","url":null,"abstract":"<p><p>Drug discovery is a tedious process that takes a long time and incurs high costs in developing an approved drug for clinical use. The long time and high expenditure are due to various phases of drug discovery and do not guarantee the success of the drug for clinical use, and about 90% of potential drug candidates suffer failure in phase-I clinical trials. The drug molecule qualifying for phase I clinical trial after passing through the preclinical stages is a significant milestone for both research institutes and pharmaceutical companies. Therefore, there is a need to explore alternatives for the drug discovery process. In this regard, Artificial Intelligence may provide significant assistance in different processes of drug discovery. This review discusses the applications of AI in diverse and prominent processes of drug discovery, like identification of a diseased state, identification of target, development of lead compounds, virtual screening, and drug toxicity. AI has proved its potential in the cheaper, easier, and timely development of drugs for different ailments. The application of AI not only enhances the quality of the drug development process but also assures better safety in the treatment and diagnosis of disease. AI introduces automation in drug development and clinical trials, minimizing the chances of human error. Focusing on the quality and quantity of the data, ethical consideration of the patient data may help in revolutionizing the process of synthetic drug development and treatment.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herbal Creams in Dermatology: Efficacy, Safety, Formulation, and Regulatory Considerations.","authors":"Raj Kamal, Abhishek Chauhan, Thakur Gurjeet Singh, Sonia Dhiman, Ankit Awasthi","doi":"10.2174/0113816128456608260722083213","DOIUrl":"https://doi.org/10.2174/0113816128456608260722083213","url":null,"abstract":"<p><p>Herbal creams have gained significant prominence in dermatology for their safety, sustainability, and biologically active alternatives to conventional chemical-based formulations. Composed of plant-derived bioactive compounds, these preparations exhibit diverse pharmacological properties, including antiinflammatory, antimicrobial, antioxidant, and wound-healing effects. Key botanicals such as Aloe vera, turmeric, chamomile, tea tree oil, calendula, and liquorice contribute to the management of various skin disorders, including eczema, psoriasis, acne, and chronic wounds. Incorporation of advanced formulation strategies such as liposomes, nanoemulsions, and nanostructured lipid carriers has further enhanced dermal penetration, bioavailability, and therapeutic outcomes of herbal actives. Despite these advancements, concerns persist regarding the stability, purity, and safety of herbal creams, as natural origin alone does not guarantee the absence of adverse effects or contamination. Regulatory inconsistencies across global markets further complicate quality assurance, emphasising the need for harmonised guidelines encompassing Good Manufacturing Practices (GMP), Good Agricultural and Collection Practices (GACP), and advanced analytical validation. Sustainable sourcing, scientific standardisation, and clinical substantiation are essential to ensure reproducibility and consumer safety. The convergence of phytochemistry, nanotechnology, and regulatory science is poised to establish herbal creams as effective, evidence-based therapeutic options in modern dermatological practice.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-CAS9-Mediated Genetic Enhancement and Metabolic Engineering of Medicinal Crops: An Integrative Review.","authors":"Lokendra Soni, Harshita Singhai, Sunny Rathee, Sakshi Soni, Umesh K Patil","doi":"10.2174/0113816128481888260727052548","DOIUrl":"https://doi.org/10.2174/0113816128481888260727052548","url":null,"abstract":"<p><p>This descriptive review comprehensively examines recent advances in the genetic improvement of medicinal plants through the application of CRISPR-Cas9 genome-editing technology, highlighting its transformative potential in biotechnology and pharmacognosy. The review systematically discusses the fundamental principles of the CRISPR-Cas9 system, including its mechanism of action, delivery strategies, and comparative advantages over conventional genome-editing techniques. Particular emphasis is placed on the genetic enhancement of medicinal plant species to improve the qualitative and quantitative production of bioactive secondary metabolites through targeted modification of key genetic traits. In addition, the review explores the application of CRISPR-Cas9 for enhancing stress tolerance, environmental adaptability, and the regulation of metabolic biosynthetic pathways. Representative case studies involving medicinal plant species, including Artemisia annua and Catharanthus roseus, are critically evaluated to demonstrate the successful implementation of CRISPR-Cas9-mediated genome editing. Furthermore, the review discusses the synergistic integration of metabolic engineering, omics technologies, and synthetic biology for optimizing secondary metabolite biosynthesis. Finally, it highlights the growing role of next-generation genome-editing technologies, particularly CRISPR-Cas9, in advancing sustainable phytopharmaceutical and nutraceutical research and facilitating the development of high-value medicinal plant resources.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Artificial Intelligence into Biopharmaceutical Formulation and Development: A Critical Review.","authors":"Samarth Chaudhary, Shikha Baghel Chauhan, Rajan Swami, Indu Singh","doi":"10.2174/0113816128486398260721142703","DOIUrl":"https://doi.org/10.2174/0113816128486398260721142703","url":null,"abstract":"<p><strong>Objective: </strong>This review critically examines the integration of artificial intelligence (AI) methods into biopharmaceutical formulation science, with emphasis on core formulation challenges including solubility, stability, aggregation, viscosity, excipient compatibility, nanocarrier optimization, release behaviour, and manufacturability.</p><p><strong>Method: </strong>A structured literature review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Relevant peer-reviewed studies were selected using predefined inclusion and exclusion criteria and evaluated based on methodological quality and reported outcomes.</p><p><strong>Result: </strong>The reviewed studies demonstrate that AI improves the prediction of critical formulation properties, optimizes formulation design, and enhances manufacturing processes. However, its performance depends on data quality, model validation, and interpretability.</p><p><strong>Discussion: </strong>AI has the potential to accelerate formulation development and improve product quality through predictive modelling and intelligent process optimization. Nevertheless, challenges related to data availability, regulatory acceptance, and model transparency remain barriers to broader implementation.</p><p><strong>Conclusion: </strong>AI represents a transformative enabler for biopharmaceutical formulation science. Realizing its full potential requires FAIR data ecosystems, explainable AI (XAI) frameworks, and adaptive regulatory guidance aligned with ICH Q8-Q12 and GAMP 5 standards.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Ketamine in Major Depressive Disorder: Pharmacological Insights and Clinical Evidence.","authors":"Prachi Tayal, Rina Das, M U Khan, Dinesh Kumar Mehta","doi":"10.2174/0113816128462317260721102058","DOIUrl":"https://doi.org/10.2174/0113816128462317260721102058","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is one of the leading causes of disability globally, and conventional monoaminergic antidepressants often have a slow onset and limited efficacy. About onethird of patients suffer from treatment-resistant depression (TRD), which emphasizes the urgent need for alternative therapies. This review aims to systematically evaluate the available data about ketamine's involvement in depression, with particular attention to its pharmacological properties, modes of action, clinical effectiveness, safety profile, and potential as a next-generation antidepressant treatment.</p><p><strong>Methods: </strong>The databases ScienceDirect and PubMed/MEDLINE were searched extensively for relevant literature. Ketamine's pharmacodynamics, clinical results, safety, and mechanistic insights in Major depressive disorder (MDD) and treatment-resistant depression (TRD) were all investigated in eligible studies. Particular focus was given to its reported side effects and molecular mechanisms.</p><p><strong>Results: </strong>The FDA's 2019 clearance of intranasal esketamine further cemented the paradigm shift in treatment for treatment-resistant depression (TRD), which has been revolutionized by ketamine's ability to provide quick and long-lasting symptom relief. A strong neurobiological cascade underlies its therapeutic impact: NMDA receptor antagonistic action causes glutamate-AMPA activation to spike, which in turn activates the BDNF-mTORC1 signalling pathway, promoting fast synaptogenesis and reversing neuronal atrophy in the prefrontal cortex. Although dissociative side effects and cardiovascular risks now limit clinical use, the field is moving toward next-generation drugs like (2R,6R)-hydroxynorketamine. In order to create safer and more easily accessible rapid-acting antidepressants, these metabolites seek to eliminate the negative psychoactive character of ketamine while using its transformative neuroplasticity.</p><p><strong>Conclusion: </strong>When conventional treatments are ineffective for treating treatment-resistant depression, ketamine offers quick and strong results, marking a paradigm change in psychiatric care. To optimise longitudinal dosage regimens, assess long-term safety profiles, and develop next-generation analogues that maintain neuroplastic benefits while reducing side effects, further investigation is necessary.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}