Current drug metabolism最新文献

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Temperature-sensitive Hydrogel: An Effective Treatment for Nasal Drug Delivery Targeting the Brain. 温度敏感水凝胶:一种针对大脑的鼻腔给药的有效治疗方法。
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2025-05-06 DOI: 10.2174/0113892002365157250422114917
Doudou Li, Liping Chen, Yidan Chen, Lin Jiang, Rong Wang, Wenbin Li
{"title":"Temperature-sensitive Hydrogel: An Effective Treatment for Nasal Drug Delivery Targeting the Brain.","authors":"Doudou Li, Liping Chen, Yidan Chen, Lin Jiang, Rong Wang, Wenbin Li","doi":"10.2174/0113892002365157250422114917","DOIUrl":"https://doi.org/10.2174/0113892002365157250422114917","url":null,"abstract":"<p><p>The brain is highly protected by physiological barriers, in which the blood-brain barrier restricts the entry of most drugs. Intranasal drug delivery is a non-invasive way of drug delivery, which can cross the blood-brain barrier and achieve direct and efficient targeted delivery to the brain. Therefore, it has great po-tential in application to the treatment of brain diseases. Temperature-sensitive hydrogels undergo a solution-gel transition with temperature change, and the gel form has good mucosal adsorption properties in the nasal cavity, which is commonly used for targeted delivery of drugs for brain diseases. In this article, by introducing the transport mechanism of brain targeting after nasal administration, combined with the prescription design and basic performance study of temperature-sensitive nasal hydrogel, we summarized the research on the role that temperature-sensitive hydrogel plays brain targeting after via nasal administration, aiming to provide a reference for the development of therapeutic drugs for cerebral diseases and their clinical application. A graph-ical summary is shown in Fig. (1).</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962667","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}
引用次数: 0
Antioxidant Potential of Gallic Acid Prevents Di-2-ethyhexyl Phthalate-induced Inhibition of Osteogenic Differentiation. 没食子酸的抗氧化潜能阻止邻苯二甲酸二乙己酯诱导的成骨分化抑制。
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2025-04-28 DOI: 10.2174/0113892002338014250416100651
Abnosi Mohammad Hussein, Parvaz Mahrokh
{"title":"Antioxidant Potential of Gallic Acid Prevents Di-2-ethyhexyl Phthalate-induced Inhibition of Osteogenic Differentiation.","authors":"Abnosi Mohammad Hussein, Parvaz Mahrokh","doi":"10.2174/0113892002338014250416100651","DOIUrl":"https://doi.org/10.2174/0113892002338014250416100651","url":null,"abstract":"<p><strong>Objective: </strong>Di-2-ethylhexylphthalate (DEHP) is utilized as a plasticizer in polyvinylchloride products (PVC). When medical devices like blood bags, tubes, and syringes are employed, DEHP leaches out of the PVC polymers and enters biological fluids through non-covalent binding. The presence of DEHP in peripheral blood leads to contamination of bone marrow. Previous research has demonstrated that this chemical induces oxidative stress, which adversely affects the viability and osteo-differentiation of bone marrow mesenchymal stem cells (BMSCs). Hence, our current study aims to utilize gallic acid (GA), a natural antioxidant, to alleviate the inhibitory effects of DEHP on BMSCs' osteogenic differentiation.</p><p><strong>Materials and methods: </strong>In osteogenic media, BMSCs extracted from Wistar rats were treated with 0.25 μM of GA and 100 μM of DEHP individually and in combination for 20 days. Then viability, total protein, malondialdehyde (MDA), total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD), alkaline phosphatase activity, production of collagen1A1 protein as well as expression of Bmp2 and 7, Smad1, Runx2, Oc, Alp, Col-1a1 genes were investigated.</p><p><strong>Results: </strong>The viability and differentiation ability of BMSCs was significantly (p<0.0001) decreased by DEHP, while GA significantly (P<0.0001) ameliorated the effect of DEHP. DEHP caused a significant decrease (P<0.0001) in the total protein and collagen-1A1 concentration, TAC and activity of antioxidant enzymes, but significantly (P<0.001) increased MDA level. In addition, DEHP caused a significant decrease in the expression of osteo-related genes. In the co-treatment group, GA mitigated the toxic effects of DEHP compared to the control group by inhibiting DEHP-induced oxidative stress and enhancing cell viability and osteo-differ-entiation properties.</p><p><strong>Conclusion: </strong>These results confirm that GA reduces the negative effects of DEHP on the osteo-differentiation of BMSCs at the cellular level. However, further studies are necessary to validate these findings.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967286","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}
引用次数: 0
A Data Mining Approach on Polypharmacy and Drug-drug Interactions of Common Diabetes Medications. 常见糖尿病药物多药及药物相互作用的数据挖掘方法。
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2025-04-17 DOI: 10.2174/0113892002358291250401190533
Jyotsana Dwivedi, Shubhi Kaushal, Pranay Wal, Darshan J C, Ankita Sharma, Deepak Nathiya, Amin Gasmi
{"title":"A Data Mining Approach on Polypharmacy and Drug-drug Interactions of Common Diabetes Medications.","authors":"Jyotsana Dwivedi, Shubhi Kaushal, Pranay Wal, Darshan J C, Ankita Sharma, Deepak Nathiya, Amin Gasmi","doi":"10.2174/0113892002358291250401190533","DOIUrl":"https://doi.org/10.2174/0113892002358291250401190533","url":null,"abstract":"<p><strong>Background: </strong>When managing diabetes, polypharmacy the use of several drugs simultaneously to obtain the best possible glucose control is typical. Drug-drug interactions (DDIs), which can result in side effects and reduced treatment efficacy, have increased.</p><p><strong>Objective: </strong>This study evaluated the data mining approach of polypharmacy-based drug-drug interactions for common diabetes medication.</p><p><strong>Methods: </strong>To identify publications that met the inclusion criteria, several scientific reviews and research papers were searched, including Scopus, Web of Science, Google Scholar, PubMed, Science Direct, Springer Link, and NCBI, using keywords such as diabetes, drug-drug interaction, polypharmacy, data mining, and herbal interaction.</p><p><strong>Results: </strong>Many important drug-drug interactions among popular anti-diabetic drugs have been identified using data mining. Using iodinated contrast media and metformin together increased the risk of lactic acidosis, and using NSAIDs and sulfonylureas simultaneously increased the risk of hypoglycemia. A higher incidence of DDIs was found in an analysis of elderly individuals and those with several comorbidities. Predictive models have demonstrated high sensitivity and accuracy in detecting possible DDIs from patient and drug data.</p><p><strong>Conclusion: </strong>Finding and evaluating DDIs in polypharmacy related to diabetes care are made possible through data mining. These results could potentially improve patient safety by influenc-ing more individualized and cautious prescription techniques. The improvement of these methods and their application in standard clinical practice should be the main goal of future studies.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984097","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}
引用次数: 0
Rapid and Comprehensive Identification of Vincosamide Metabolites in vitro and in vivo in Rats by Ultra-High Performance Liquid Chromatography-Quadrupole- Exactive Orbitrap-High Resolution Mass Spectrometry. 超高效液相色谱-四极杆-精确轨道-高分辨质谱法快速综合鉴定大鼠体内体外维萨胺代谢物。
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2025-04-16 DOI: 10.2174/0113892002351614250401153450
Aichun Gao, Hongjin Wang, Xiaoge Cheng, Caihong Li, Lixin Sun
{"title":"Rapid and Comprehensive Identification of Vincosamide Metabolites in vitro and in vivo in Rats by Ultra-High Performance Liquid Chromatography-Quadrupole- Exactive Orbitrap-High Resolution Mass Spectrometry.","authors":"Aichun Gao, Hongjin Wang, Xiaoge Cheng, Caihong Li, Lixin Sun","doi":"10.2174/0113892002351614250401153450","DOIUrl":"https://doi.org/10.2174/0113892002351614250401153450","url":null,"abstract":"<p><strong>Background: </strong>Vincosamide, an indole alkaloid extracted from Nauclea officinalis, exhibits a range of pharmacological activities, such as anti-tumor, antibacterial, and anti-inflammatory properties. However, despite its promising therapeutic applications, there is a notable gap in research focused on the metabolic pathways of vincosamide.</p><p><strong>Objective: </strong>This study aims to investigate the metabolism of vincosamide both in vitro and in vivo in rats, and to elucidate its metabolic pathways.</p><p><strong>Methods: </strong>Samples of liver microsomal incubation, plasma, bile, urine, and feces following vincosamide ad-ministration were analyzed by ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap-high resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap HRMS). The collected data were analyzed using Compound Discovery 3.2 software and the molecular network method. The metabolites identified through these methodologies were subsequently validated using Xcalibur 4.1 software, which provided infor-mation on retention times, parent ions, and characteristic fragment ions.</p><p><strong>Results: </strong>A total of 37 metabolites were identified, including 8 in vitro and 32 in vivo (3 in plasma, 7 in bile, 22 in urine, and 17 in feces). While the metabolism of vincosamide differs in vitro and in vivo in rats, the type of metabolic reaction that occurs is well-defined. The predominant metabolic pathways are oxidation, reduc-tion, deglycosylation, hydration, glucuronidation, methylation, sulfation, glycine conjugation, cysteine conju-gation, taurine conjugation, and complex reactions.</p><p><strong>Conclusion: </strong>This study elucidates the metabolism of vincosamide in vitro and in vivo in rats, thereby expand-ing the metabolite profile of vincosamide. These findings provide a foundation for the potential development of new drugs based on vincosamide.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968712","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}
引用次数: 0
Expression, Function, and Regulation of ABCG2 on the Intestinal Epithelial Barrier Permeability. ABCG2对肠上皮屏障通透性的表达、功能及调控
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2025-04-11 DOI: 10.2174/0113892002368449250331144821
Ping Shi, Lianhua Tang, Fei Yin, Hong Guo, Jianhui Liu
{"title":"Expression, Function, and Regulation of ABCG2 on the Intestinal Epithelial Barrier Permeability.","authors":"Ping Shi, Lianhua Tang, Fei Yin, Hong Guo, Jianhui Liu","doi":"10.2174/0113892002368449250331144821","DOIUrl":"https://doi.org/10.2174/0113892002368449250331144821","url":null,"abstract":"<p><p>Human breast cancer resistance protein (BCRP, gene symbol ABCG2) is an ATP-binding cassette (ABC) efflux transporter that is highly expressed on the apical membranes of intestinal epithelium and contributes to the absorption, distribution, and elimination of xenobiotics and the efflux of endogenous molecules. Also, the intestinal epithelial monolayer is the largest interface and the most important functional barrier between the internal environment and the systemic circulation. Extensive studies have demonstrated that intestinal ABCG2 of humans and rodents plays a crucial role in limiting absorption of xenobiotics, which are ABCG2 transport substrates, in the small intestine by mediating distribution in the intestinal epithelial barrier. Therefore, changes in the expression, function and activity of ABCG2 in the intestinal epithelial barrier play important roles in drug response and side effects. In this review, we specifically summarize the current research progress of ABCG2 in intestinal drug transport, intestinal urate excretion and intestinal barrier dysfunction, and its role in altering the intestinal epithelial barrier permeability in human intestinal disorder.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956345","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}
引用次数: 0
Exploring the Gut-Brain Axis: Microbiome Contributions to Pathophysiology of Attention Deficit Hyperactivity Disorder and Potential Therapeutic Strategies. 探索肠脑轴:微生物组对注意缺陷多动障碍病理生理的贡献和潜在的治疗策略。
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2025-04-08 DOI: 10.2174/0113892002361676250325082424
Manasi Phatak, Bhavi Nair, Urvashi Soni, Rohini Pujari
{"title":"Exploring the Gut-Brain Axis: Microbiome Contributions to Pathophysiology of Attention Deficit Hyperactivity Disorder and Potential Therapeutic Strategies.","authors":"Manasi Phatak, Bhavi Nair, Urvashi Soni, Rohini Pujari","doi":"10.2174/0113892002361676250325082424","DOIUrl":"https://doi.org/10.2174/0113892002361676250325082424","url":null,"abstract":"<p><p>Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by symptoms of hyperactivity, inattention, and impulsivity, significantly impacting individuals' daily functioning and quality of life. This manuscript explores the intricate relationship between the gut microbiome and ADHD, emphasizing the role of the gut-brain axis, a bidirectional communication pathway linking the central nervous system (CNS) and the gastrointestinal tract (GIT). The composition of gut microbiota influences several physiological processes, including immune function, metabolism, and the production of neuroactive metabolites, which are critical for cognitive functions such as memory and decision-making. The review discusses alternative therapeutic options, including dietary modifications, synbiotics, and specific diets like the ketogenic diet, which may offer promising outcomes in managing ADHD symptoms. Further research is necessary to establish the efficacy and mechanisms of action of synbiotics and dietary interventions, despite preliminary studies suggesting their potential benefits. This review article aims to provide a comprehensive overview of the current understanding of the gut microbiome's impact on ADHD, highlighting the need for continued investigation into innovative treatment strategies that leverage the gut-brain connection.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956289","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}
引用次数: 0
Prediction of Pharmacokinetics of Valeric Acid: Alternative Tool to Minimize Animal Studies. 戊酸药代动力学预测:减少动物实验的替代工具。
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2025-03-19 DOI: 10.2174/0113892002352975250310045810
Bindu Kumari, Dhananjay Kumar Singh, Ravi Bhushan Singh, Gireesh Kumar Singh
{"title":"Prediction of Pharmacokinetics of Valeric Acid: Alternative Tool to Minimize Animal Studies.","authors":"Bindu Kumari, Dhananjay Kumar Singh, Ravi Bhushan Singh, Gireesh Kumar Singh","doi":"10.2174/0113892002352975250310045810","DOIUrl":"https://doi.org/10.2174/0113892002352975250310045810","url":null,"abstract":"<p><strong>Background: </strong>The use of computer-aided toxicity and Pharmacokinetic (PK) prediction studies are of significant interest to pharmaceutical industries as a complementary approach to traditional experimental methods in predicting potential drug candidates.</p><p><strong>Methods: </strong>In the present study, in-silico pharmacokinetic properties (ADME), drug-likeness, and toxicity profiles of valeric acid were examined using SwissADME and ADMETlab web tools.</p><p><strong>Results: </strong>The drug-likeness prediction results revealed that valeric acid adheres to the Lipinski rule, Pfizer rule, and GlaxoSmithKline (GSK) rule. From a pharmacokinetic perspective, valeric acid is anticipated to have the best absorption profile including cell permeability and bioavailability. Plasma Protein Binding (PPB) and Blood-Brain Barrier (BBB) permeability may have a positive effect on Central Nervous System modulating (CNS). There is a minimal chance of it being a substrate for cytochrome P2D6 (CYP). Except for a \"very slight risk\" for eye corrosion and eye irritation, none of the well-known toxicities in valeric acid were anticipated, which was compatible with wet-lab data. The molecule possesses no environmental hazard as analyzed with common indicators such as bio-concentration factor and LC50 for fathead minnow and daphnia magna. The toxicity parameters identified valeric acid as nontoxic to androgen receptors, antioxidant response element, mitochondrial membrane receptor, heat shock element, and tumor suppressor protein (p53), except Peroxisome Proliferator-Activated Receptor- gamma (PPAR-γ) was found to be medium toxicity. However, no toxicophores were found out of seven parameters.</p><p><strong>Conclusion: </strong>Overall, the ADMETLab evaluated that valeric acid has favorable pharmacokinetic and drug-likeness profiles, making it a promising drug candidate for new drug development.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662957","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}
引用次数: 0
Effect of Wuzhi Capsule (WZC) on the Pharmacokinetics of Tacrolimus in Renal Transplantation Recipients. 五脂胶囊对肾移植受者他克莫司药动学的影响。
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2025-03-19 DOI: 10.2174/0113892002320686250310054152
Weiyue Zhang, Ruidong Wang, Lin Li, Jiani Chen, Jingwen Zhai, Wei Wang, Shiyi Liu, Hong Liu, Hua Wei, Shu Han
{"title":"Effect of Wuzhi Capsule (WZC) on the Pharmacokinetics of Tacrolimus in Renal Transplantation Recipients.","authors":"Weiyue Zhang, Ruidong Wang, Lin Li, Jiani Chen, Jingwen Zhai, Wei Wang, Shiyi Liu, Hong Liu, Hua Wei, Shu Han","doi":"10.2174/0113892002320686250310054152","DOIUrl":"https://doi.org/10.2174/0113892002320686250310054152","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown that WZC can increase tacrolimus blood concentration when co-administered. However, limited knowledge exists regarding the pharmacokinetics of both tacrolimus and the bioactive lignans in WZC when administered simultaneously in renal transplantation patients.</p><p><strong>Aims: </strong>This study aimed to investigate the pharmacokinetics of tacrolimus and multiple bioactive lignans in Wuzhi capsule (WZC) when co-administered with 5 bioactive components in renal transplantation recipients.</p><p><strong>Objective: </strong>The objective of this study was to develop a method for simultaneous quantification of tacrolimus and multiple bioactive lignans in WZC using liquid-liquid extraction followed by LC-MS/MS analysis.</p><p><strong>Method: </strong>A liquid-liquid extraction method combined with LC-MS/MS analysis was developed for simultane-ous quantification of tacrolimus and multiple bioactive lignans in WZC. Human whole blood samples were analyzed, and the accuracy and precision of the method were evaluated.</p><p><strong>Result: </strong>The developed method showed good linearity and accuracy for the quantification of tacrolimus and bioactive lignans in WZC. Pharmacokinetic analysis revealed significant effects of WZC co-administration on both V/F and CL/F in renal transplantation patients.</p><p><strong>Conclusion: </strong>This study demonstrated that simultaneous administration of WZC had notable effects on the pharmacokinetics of tacrolimus and bioactive lignans in renal transplantation patients. The developed method proved to be reliable and sensitive for determining the whole blood concentrations of tacrolimus and WZC, making it suitable for pharmacokinetic studies in transplant patients.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662955","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}
引用次数: 0
Comparative in Vitro Metabolic Profile Study of Five Cathinone Derivatives. 五种卡西酮衍生物体外代谢谱的比较研究。
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2025-03-17 DOI: 10.2174/0113892002348484250309011657
Zexuan Li, Sufang Xiang, Tian Zheng, Guoping Wu, Liang Wu
{"title":"Comparative in Vitro Metabolic Profile Study of Five Cathinone Derivatives.","authors":"Zexuan Li, Sufang Xiang, Tian Zheng, Guoping Wu, Liang Wu","doi":"10.2174/0113892002348484250309011657","DOIUrl":"https://doi.org/10.2174/0113892002348484250309011657","url":null,"abstract":"<p><strong>Background: </strong>Cathinone derivatives as new psychoactive substances have attracted worldwide attention in recent years. They have strong excitatory effects on the human central nervous system, which is extremely abusive and harmful. As they are easy to be structurally modified, and rapidly metabolized and excreted after taken, clarifying their metabolic profile is of significant importance to provide useful information for their identification or forensic purposes.</p><p><strong>Objective: </strong>In this paper, a comparative in vitro metabolic profile study of five cathinone derivatives (4/3/2- methylmethcathinone and 4/3-methoxymethcathinone) was performed, including their metabolic stability in the simulated gastrointestinal tract, mass spectrometry fragmentation behavior, possible metabolic pathways and metabolites in human liver microsomal incubation system, and revealing the key metabolic enzyme isoforms involving in their biotransformation.</p><p><strong>Methods: </strong>In vitro incubation was performed in simulated gastric/intestinal fluid and human liver microsomes, fragmentation behavior study and metabolite identification were investigated by LC-Q-TOF/MS, and metabolic stability study, along with metabolic enzyme screening were analyzed using LC-MS/MS.</p><p><strong>Results: </strong>Almost all the cathinone derivatives tested were stable in the simulated gastric/intestinal fluid; characteristic fragmentation pathway and diagnostic fragment ions of the cathinone derivatives were analyzed; the key metabolic pathways of 4/3-methylmethcathinone and 4/3-methoxymethcathinone revealed were hydroxylation and demethylation, which were catalyzed by CYP2D6. The methyl-substituted position would significantly affect the metabolic pathway of the methylmethcathinone.</p><p><strong>Conclusion: </strong>This study revealed the mass spectral fragmentation pattern and the in vitro metabolic behavior of the selected cathinone derivatives, providing meaningful information and scientific evidence in predicting their metabolic potential in vivo, and also promoting their analysis, detection, and clinical use.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656378","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}
引用次数: 0
Transformative CRISPR-Cas9 Technologies: A Review of Molecular Mechanisms, Precision Editing Techniques, and Clinical Progress in Sickle Cell Disease. 转化CRISPR-Cas9技术:镰状细胞病的分子机制、精确编辑技术和临床进展综述
IF 2.1 4区 医学
Current drug metabolism Pub Date : 2025-03-05 DOI: 10.2174/0113892002356293250225094826
Komal, Prabhjot Kaur, Nidhi Arora, Jyotiram A Sawale, Amandeep Singh
{"title":"Transformative CRISPR-Cas9 Technologies: A Review of Molecular Mechanisms, Precision Editing Techniques, and Clinical Progress in Sickle Cell Disease.","authors":"Komal, Prabhjot Kaur, Nidhi Arora, Jyotiram A Sawale, Amandeep Singh","doi":"10.2174/0113892002356293250225094826","DOIUrl":"https://doi.org/10.2174/0113892002356293250225094826","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a hereditary blood disorder resulting from the production of distorted hemoglobin molecules that cause red blood cells to adopt a sickle or crescent-like shape. This disease affects millions of people, particularly those of African, Mediterranean, Middle Eastern, or South Asian descent. In recent years, however, advancements in the CRISPR-Cas9 gene-editing systems have surged. CRISPR stands for clustered regularly interspaced short palindromic repeats, referring to a specific organization of short, partially repeated DNA sequences in prokaryotic genomes. The CRISPR-Cas9 technique is based on the type II CRISPR system of bacteria and involves the Cas9 nuclease, which is targeted to a particular genome section with the help of single-guide RNA. Initially used for random mutations and small sequence alterations, genome editing methods have advanced to achieve large-scale DNA segment manipulation. The BE and PE-- type CRISPR-Cas9 genome editing variants provide new therapeutic options for genetic disorders, improving patients' prognosis. Curative gene editing using CRISPR-Cas9 technology to correct HBB gene mutations that cause SCD represents a revolutionary therapeutic development. These advances bring new hope to patients with previously untreatable diseases, potentially offering a future where genetic disorders can be addressed at their roots. A major objective of CRISPR technology is to enhance its precision and speed, both critical for effective gene editing. This review focuses on molecular mechanisms of CRISPR-Cas9 technology, CRISPR-- Cas9-based approaches for HBB gene modification, clinical trials, patients with sickle cell disease, and advances in CRISPR technology for sickle cell disease.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566373","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}
引用次数: 0
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