Current Reviews in Clinical and Experimental Pharmacology最新文献

{"title":"Post-Ingestion Blood Hydrogen Kinetics Following Oral Hydrogen-Rich Water Intake in Healthy Adults: A Pilot Pharmacokinetic Study.","authors":"David Nedeljkovic, Nikola Todorovic, Dejan Javorac, Bogdan Andjelic, Milan Vranes, Sergej M Ostojic","doi":"10.2174/0127724328507426261006065812","DOIUrl":"https://doi.org/10.2174/0127724328507426261006065812","url":null,"abstract":"<p><strong>Introduction: </strong>Molecular hydrogen (H2) has gained attention as a therapeutic agent due to its antioxidant and anti-inflammatory properties. However, human Pharmacokinetic (PK) data remain limited, particularly for Hydrogen-Rich Water (HRW). This study aimed to characterize blood hydrogen kinetics following oral HRW intake in healthy adults.</p><p><strong>Methods: </strong>Twelve healthy participants (mean age 28.8 ± 3.8 years; BMI 23.4 ± 3.2 kg/m²; 50% female) were enrolled in the study. After an overnight fast, participants consumed a single dose of HRW. Blood samples were collected at baseline and at multiple time points up to 120 minutes postingestion. Hydrogen concentrations were measured using a Clark-type microsensor. PK parameters were calculated using non-compartmental analysis, and time-dependent changes were assessed using linear mixed-effects modeling.</p><p><strong>Results: </strong>Baseline hydrogen concentration was 0.25 ± 0.05 μg/L. Peak concentration (Cmax) reached 0.83 ± 0.18 μg/L at 42.9 ± 8.4 minutes (Tmax). The elimination half-life was 144.8 ± 41.7 minutes, and total systemic exposure (AUC₀-∞) was 128.6 ± 27.1 μg/L·min. Hydrogen levels were significantly elevated at 15, 60, and 90 minutes compared to baseline. Notable inter-individual variability was observed, and no sex-related differences were detected.</p><p><strong>Discussion: </strong>Oral HRW intake resulted in measurable systemic hydrogen exposure, with a biphasic concentration pattern, suggesting rapid absorption possibly followed by redistribution. Observed concentrations approached proposed minimal effective levels but were not sustained, raising questions about optimal dosing strategies.</p><p><strong>Conclusion: </strong>HRW ingestion produces detectable and biologically relevant increases in blood hydrogen levels. These findings support HRW as a viable route of H2 administration and provide a foundation for future studies investigating dosing, kinetics, and therapeutic applications.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Regulatory Frameworks for Cannabinoids and Cannabis-Based Medicinal Products: A Comprehensive Review of Contemporary Approaches and Challenges.","authors":"Shalini Dwivedi, Jeanine Giarolla Vargas, Samridhi Lal","doi":"10.2174/0127724328501726260907075438","DOIUrl":"https://doi.org/10.2174/0127724328501726260907075438","url":null,"abstract":"<p><strong>Introduction: </strong>Over the last decade, the regulation of cannabinoids and cannabis-based medicinal products has undergone significant transformation, determined by growing evidence of their therapeutic value and increasing concerns about safety, misuse, and product diversion. The objective of this review was to examine current regulatory frameworks across major jurisdictions from a public health policy perspective, highlighting how different approaches seek to balance patient access with health protection.</p><p><strong>Methods: </strong>This review followed a targeted literature search in scientific databased (PubMed and Google Scholar) to identify publications in English language addressing the evolution of medical cannabis and cannabinoid policies, with particular emphasis on the regulatory frameworks in various countries. The identified literature was qualitatively analyzed to evaluate the relationship between international policy developments and the evolution of national medical cannabis regulations and research activities.</p><p><strong>Results: </strong>This review identified three primary regulatory models: traditional pharmaceutical approval pathways that require robust clinical evidence; alternative access mechanisms, e.g., compassionate- use and special access programs; and regulatory systems which have varying levels of regulatory oversight, quality control, and patient protections, especially the vulnerable population.</p><p><strong>Discussion: </strong>While there has been an increasing global acceptance of cannabinoid-based therapies, considerable differences in regulatory requirements remain across countries. Such a fragmentation creates barriers to clinical research on cannabinoids and cannabis products, obscures patient access, and limits effective public health surveillance. Additionally, challenges related to product quality, standardization, labeling accuracy, and pharmacovigilance are particularly obvious for botanical cannabis products, where regulatory expectations often differ from those applied to conventional medicines. At the same time, innovative regulatory developments are emerging.</p><p><strong>Conclusion: </strong>The review highlights that a greater international regulatory harmonization, stronger quality assurance frameworks, and evidence-based monitoring systems are required for cannabinoids and cannabis products. These aspects are crucial for protecting public health, supporting scientific research, and enabling the responsible integration of cannabinoid-based therapies into modern healthcare systems.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin as an Emerging Candidate for Diabetic Retinopathy, Agerelated Macular Degeneration and Glaucoma Pharmacotherapy: Evidence and Perspectives.","authors":"Marianne Levon Shahsuvaryan","doi":"10.2174/0127724328519947260917114932","DOIUrl":"https://doi.org/10.2174/0127724328519947260917114932","url":null,"abstract":"<p><p>Varying degrees of visual impairment up to complete blindness are widespread and represent a public health problem with a highly demarсated escalation. Currently, the leading causes of blindness are Diabetic Retinopathy (DR), Age-Related Macular Degeneration (AMD), and glaucoma, with an obvious exponential enlargement of vulnerable population groups as a result of urbanization followed by lifestyle changes and growth of the aging population. Management of these diseases is still challenging. The development of intraocular therapy with antiangiogenics or Vascular Endothelial Growth Factor inhibitors (anti-VEGF) opens a new avenue in eye disease treatment; however, despite these advances, new concerns are raised. DR, AMD, and glaucoma represent diseases with bilateral involvement, which underscores a need for oral systemic preventive therapy targeting both eyes simultaneously, as a cost-effectively optimized approach. At the same time, there is a need for a multi-target drug with preventive and therapeutic potential not only for eye diseases, but also for systemic diseases in patients with multimorbidity. Continued research has the potential to enhance druggability of the leading causes of blindness. A growing body of evidence suggests that metformin, as a drug with multimodal activity, has good preventive and therapeutic potential, opening a new avenue in ocular pharmacotherapy.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Melatonin for Sleep Disorders in Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.","authors":"Mohammad Mehdi Abbasi, Shiva Pasha, Farbod Khosravi, Amir Reza Boskabadi, Faezeh Jamshidi, Zahra Rahimian, Pooya Eini, Yashar Talebi, Mohammadsadegh Jafari, Sara Bahramabadinejad, Afsaneh Safarian, Hossein Soltaninejad, Mohammad Rahmanian","doi":"10.2174/0127724328470308260825053321","DOIUrl":"https://doi.org/10.2174/0127724328470308260825053321","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Sleep disruption is common among patients with malignancy and may worsen quality of life, treatment tolerance, and symptom burden. Melatonin is a circadianregulating hormone with a favorable safety profile and potential sleep-promoting effects. This metaanalysis and systematic review evaluated the safety and efficacy of melatonin for sleep-related outcomes in patients with cancer.</p><p><strong>Methods: </strong>Scopus, PubMed, Web of Science, ScienceDirect, Cochrane Library, ClinicalTrials.gov, and EMBASE were systematically searched from inception to 1 June 2026 without language or country restrictions. Randomized clinical trials comparing melatonin with placebo or an active control in patients with cancer and reporting sleep-related outcomes were eligible. Data extraction, study selection, and riskof- bias assessment using the Joanna Briggs Institute checklist were performed by two reviewers independently. Random-effects meta-analyses with Hartung-Knapp adjustment were conducted in Stata 17.0.</p><p><strong>Results: </strong>Data from seven studies were pooled in the meta-analysis, and thirteen articles were included in the systematic review. The overall effect of melatonin was insignificant (SMD = -0.85 with a 95% CI of -2.46 to 0.76) with high heterogeneity among studies (I2 = 94.5%). Subgroup analysis revealed a significant decrease in the Pittsburgh Sleep Quality Index (PSQI) in US studies (SMD = -0.57, 95% CI: [-0.99, -0.14], I2 = 31.5%). Meta-analysis of the seven PSQI components showed no significant item-level improvement with melatonin treatment. Studies using non-PSQI sleep outcomes showed mixed findings, with short-term improvement in insomnia severity in one trial but modest or non-significant effects in others.</p><p><strong>Discussion: </strong>While the overall impact of melatonin on sleep quality was not statistically significant, subgroup analyses and qualitative evidence indicate clinically relevant benefits.</p><p><strong>Conclusion: </strong>Melatonin shows promising but uncertain benefits for sleep disruptions in patients with malignancies. However, the evidence should be interpreted cautiously because of substantial clinical and statistical heterogeneity, limited sample sizes, short intervention durations, and predominantly subjective sleep measures. Larger, well-standardized randomized trials using both subjective and objective sleep assessments are needed.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Review of Factors Influencing Intrasubject Variability in Bioequivalence Studies.","authors":"Shrikrishna Bajarang Pawar, Atul N Chandu, Saravanan Devarajan","doi":"10.2174/0127724328479835260711073244","DOIUrl":"https://doi.org/10.2174/0127724328479835260711073244","url":null,"abstract":"<p><p>Intrasubject variability (ISV) in bioequivalence (BE) studies remains a critical challenge in generic drug development; however, the mechanistic determinants of this variability are not yet fully characterized. This narrative review synthesizes evidence across physicochemical, pharmacokinetic, physiological, and study design domains using a unified mechanistic framework. Our analysis identified a mechanistic hierarchy. Low solubility (BCS Class II/IV) demonstrated a 4.1-fold higher incidence of highly variable drug (HVD) compared with high-solubility classes. First-pass metabolism was observed in 83% of HVDs but only 21% of non-HVDs, making it the strongest pharmacokinetic predictor of HVD status. Subject recruitment stratified by genotyping of CYP2D6 and CYP3A5 polymorphisms reduced ISV by up to 54% in drugs primarily metabolized by these enzymes. Replicate study designs, enhanced measurement precision, and fed conditions reduced intrasubject variability (ISV) in pharmacokinetic parameters; specifically, fed conditions showed a reduction in ISV in 79.4% of comparisons, whereas multiple-dose studies did not consistently reduce ISV. A cross-population comparison revealed that ISV in drugs metabolized via CYP enzymes was consistently higher in the Mexican population than in the South Korean population. ISV in Cmax exceeded that of AUC0-t in over 80% of products, indicating that variability in absorption rate is the primary contributing factor. A four-stage mechanistic framework, termed the Intrasubject Variability (ISV) Cascade Model, was developed to describe ISV: absorption variability generation (Stage 1), amplification through first-pass metabolism (Stage 2), modulation by study design (Stage 3), and translation into bioequivalence study design requirements (Stage 4). A proposed decision tree provides structured guidance for ISV risk assessment and optimization of BE study design.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Evolution and Impact of Pharmacist-Driven Antimicrobial Stewardship Programs: A Review.","authors":"Shesham Kumari, Ranjeet Kumar, Manish Singh, Dharmendra Kumar","doi":"10.2174/0127724328472131260630070452","DOIUrl":"https://doi.org/10.2174/0127724328472131260630070452","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) continues to increase at an alarming rate worldwide. Antimicrobial Stewardship Programs (ASPs) play a critical role in mitigating the growing threat of AMR. The objective of this review is to summarize the expanding body of evidence supporting the role of clinical pharmacists as key leaders in ASPs and to highlight the ongoing evolution of their responsibilities. In recent years, the involvement of clinical pharmacists in ASPs has progressed from primarily providing logistical support to serving as essential stewardship leaders and infectious disease specialists. This evolution has been driven, in part, by the formalization of their roles through international guidelines and professional recommendations. Pharmacist-led interventions, including prospective audit and feedback, formulary restriction, dose optimization, and intravenous (IV)-to-oral antimicrobial conversion programs, have demonstrated significant improvements in clinical, microbiological, and economic outcomes. These interventions have been associated with reductions in all-cause mortality (up to a 26% relative risk reduction), shorter hospital stays (1.0- 1.6 days), decreased rates of Clostridioides difficile infection (CDI) (up to a 32% reduction), and substantial healthcare cost savings ranging from $200,000 to $400,000 annually, often yielding a favorable return on investment. Consistent reductions in CDI rates and significant economic benefits further reinforce the value of pharmacist-led stewardship initiatives. Despite these successes, challenges remain in maximizing the impact of clinical pharmacists within ASPs, including limited resources, workforce constraints, and insufficient interdisciplinary collaboration. Nevertheless, emerging opportunities such as the integration of artificial intelligence, expansion into ambulatory care settings, and the development of innovative stewardship models in resource-limited environments offer promising avenues for future growth. The transition from an individual prescribing model to a collaborative stewardship-driven approach represents a significant advancement in contemporary healthcare practice. Clinical pharmacists play a vital role in ASPs and are essential for preserving the effectiveness of antimicrobial agents, improving patient outcomes, and ensuring the sustainability of healthcare systems worldwide.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toll-Like Receptor-Mediated Neuroinflammation and Its Role in Neurocognitive Functions.","authors":"Vivek Srivastava, Suman Chakraborty, Richa Srivastava","doi":"10.2174/0127724328415188260605204430","DOIUrl":"https://doi.org/10.2174/0127724328415188260605204430","url":null,"abstract":"<p><p>Toll-like receptors (TLRs) are a family of pattern recognition receptors that recognise both pathogen-associated and damage-associated molecular patterns. While their expression was initially believed to be restricted to immune cells, accumulating evidence now demonstrates their presence across multiple neural cell types. Due to their significant involvement in neuroinflammatory and neurodegenerative processes, TLRs have garnered growing attention for their potential contributions to neurocognitive disorders, including Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and other forms of dementia. Potential treatment targets for lowering neuroinflammation and slowing the evolution of neurocognitive diseases include TLR signalling pathways, namely the MYD88-dependent and TRIF-dependent cascades. To initiate signalling, Toll-like receptors (TLRs) recruit specific adaptor molecules that activate the transcription factors NF-κB and IRFs, which regulate the induction of innate immune responses. Over the past decade, a combination of genetic, biochemical, structural, cellular, and bioinformatics approaches has been utilised to elucidate the detailed molecular mechanisms underlying TLR signalling. These studies have clarified how TLRs interact with cytosolic innate immune sensors to orchestrate effective immunological reactions. The function of different TLRs expressed in various brain immune cells and their contribution to the pathophysiology of neuroinflammation are described. This paper discusses the involvement of TLRs in autoimmune and neuroinflammatory circumstances like multiple sclerosis (MS), bacterial meningitis, viral encephalitis, stroke, Alzheimer's disease, and Parkinson's disease. It is intended for TLR biologists and immunologists studying neuroinflammation, as well as neuroscientists delving into central nervous system processes mediated by TLRs.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome Drug Interactions in Cancer Pharmacology: Mechanisms and Therapeutic Opportunities.","authors":"Arvind Kumar Patel, Neha Singh, Phool Chandra, Neetu Sachan, Pawan Kumar Goswami, Shivam","doi":"10.2174/0127724328479943260605055353","DOIUrl":"https://doi.org/10.2174/0127724328479943260605055353","url":null,"abstract":"<p><strong>Introduction: </strong>Interindividual variability in cancer therapy response cannot be fully explained by host genetics or tumor characteristics alone. Emerging evidence indicates that the gut microbiome is a critical modulator of anticancer drug metabolism, immune responses, and therapeutic outcomes, positioning it as an important determinant in cancer pharmacology.</p><p><strong>Methods: </strong>This narrative review employed a structured literature search of PubMed, Scopus, and Web of Science (2005-2025) to synthesise preclinical and clinical evidence on microbiome-drug interactions, focusing on pharmacokinetics, immune modulation, toxicity, and resistance across chemotherapy, immunotherapy, and targeted therapies.</p><p><strong>Results and discussion: </strong>The gut microbiome influences anticancer therapy through enzymatic biotransformation, immune regulation, metabolite signalling, and maintenance of intestinal barrier integrity. Clinically, favourable microbiome profiles have been associated with improved immunotherapy outcomes, with reported hazard ratios for survival ranging from ~0.5 to 0.7, while prior antibiotic exposure is linked to a 20-40% reduction in response rates. Microbial enzymes such as β- glucuronidase contribute to irinotecan-induced toxicity, affecting up to 20-40% of patients. Specific taxa, including Akkermansia muciniphila and Bifidobacterium spp., are associated with enhanced therapeutic response. Microbiome-targeted interventions, including faecal microbiota transplantation, have demonstrated response restoration in approximately 30-40% of refractory cases in early clinical studies. However, heterogeneity in microbial composition, lack of standardisation, and safety concerns limit clinical translation.</p><p><strong>Conclusion: </strong>The gut microbiome represents an adaptable determinant of cancer pharmacology. Integrating microbiome-informed strategies offers a promising pathway toward precision oncology, although robust clinical validation remains essential for routine implementation.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148266389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-Informed Precision Dosing in Pediatrics: Current Practices, Opportunities, and Challenges.","authors":"Rohith Anandan Prabakar, Abilash Reddybathini, Chandramouli Radhakrishnan, Muhasaparur Ganesan Rajanandh","doi":"10.2174/0127724328461249260523072801","DOIUrl":"https://doi.org/10.2174/0127724328461249260523072801","url":null,"abstract":"<p><p>Recent advances in pediatric pharmacokinetics highlight substantial age-dependent physiological changes that require specialised approaches to optimise efficacy and minimise adverse effects in children. This review compares pharmacokinetic differences between adults and children, traditional dosing approaches, and recent developments in Model-Informed Precision Dosing (MIPD), with a focus on Population Pharmacokinetic (PopPK) and Physiologically Based Pharmacokinetic (PBPK) modeling strategies. Recent advances in Bayesian forecasting and the integration of artificial intelligence and machine learning are highlighted for their potential to improve dosing accuracy and clinical decision-making. This article examines current regulatory perspectives on pharmacometric approaches in pediatric medication development and offers insights into evolving standards and guidelines. It also addresses key technical, logistical, and regulatory challenges and potential solutions. Based on these insights, future strategies to improve model-based precision in pediatric dosing are discussed.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opioid Receptor Independent Effects of Opioid Peptides.","authors":"Leonid N Maslov, Alexander V Mukhomedzyanov, Alisa S Slidnevskaya, Alexander S Gorbunov, Sergey V Popov, Artur Kan, Natalia V Naryzhnaya, Feng Fu, Philipp A Ilinykh, Viacheslav N Azev, Huijie Ma","doi":"10.2174/0127724328447479260426103254","DOIUrl":"https://doi.org/10.2174/0127724328447479260426103254","url":null,"abstract":"<p><p>Almost immediately after the discovery of opioid peptides and opioid receptors (ORs), reports were published that some effects of opioid peptides are independent of the activation of ORs. It was demonstrated that Des-Tyr1-fragments of opioid peptides did not interact with ORs but can exert different effects both in vivo and in vivo. They modify the functional state of the brain, the heart, the trachea, the aorta, arteries, natural killers, neutrophils, lymphocytes, and adrenal glands. It is quite obvious that non-ORs of Des-Tyr1-enkephalins, Des-Tyr1-dynorphins A, β-endorphin (2- 17), and β-endorphin (12-19) can be different. The physiological role of non-ORs of opioid peptides remains unknown because non-OR antagonists have not yet been found. It is unclear which Gproteins are coupled to non-ORs. It is unknown which intracellular messengers are involved in the effects of the activation of non-ORs by opioid peptides.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}