Current Research in Pharmacology and Drug Discovery最新文献

{"title":"Myrtenal mitigates streptozotocin-induced spatial memory deficit via improving oxido inflammatory, cholinergic and neurotransmitter functions in mice","authors":"Isaac Oluwatobi Akefe ,&nbsp;Victoria Aderonke Adegoke ,&nbsp;Ibrahim Yusuf Lamidi ,&nbsp;Matthew Phillip Ameh ,&nbsp;Enokela Shaibu Idoga ,&nbsp;Simon Azubuike Ubah ,&nbsp;Itopa Etudaye Ajayi","doi":"10.1016/j.crphar.2022.100106","DOIUrl":"10.1016/j.crphar.2022.100106","url":null,"abstract":"<div><p>The occurrence of chronic neurodegenerative disorders is on the rise, but with no effective treatment due to the paucity of information on the pathological mechanism underlying these disorders. Thus, this study investigated the role of oral administration of myrtenal in mitigating memory deficits and neuro-biochemical alterations in streptozotocin-demented mice model. Mice (n ​= ​35) were randomly allocated into five cohorts consisting of 7 mice each; Group I: Control mice received vehicle alone; Group II: streptozotocin; Group III: streptozotocin + 100 ​mg/kg myrtenal; Group IV: streptozotocin +200 ​mg/kg myrtenal; and Group V: streptozotocin ​+ ​donepezil 0.5 ​mg/kg. Data from this study demonstrated that the administration of streptozotocin (STZ) impaired spatial memory and induced alterations in markers of oxido-inflammatory response, cholinergic function, cytoarchitecture, and neurotransmitter levels in mice hippocampus. Notably, administration of myrtenal enhanced spatial memory performance in STZ-demented mice by improving the activities of endogenous antioxidant enzymes to protect the brain from oxido-inflammatory stress. Treatment with myrtenal also restored cholinergic function and stabilized the homeostasis of neurotransmitters in STZ-demented mice. The authors infer that fruits rich in myrtenal may be beneficial for treating patients living with dementia associated with Alzheimer's disease.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000268/pdfft?md5=f51bbb2d7e71d0a63efbfd94dea8f1e3&pid=1-s2.0-S2590257122000268-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45827127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Managing complex perianal disease after anti-TNF failure: Where to go next?","authors":"Clare Yzet ,&nbsp;Franck Brazier ,&nbsp;Charles Sabbagh ,&nbsp;Mathurin Fumery","doi":"10.1016/j.crphar.2022.100081","DOIUrl":"10.1016/j.crphar.2022.100081","url":null,"abstract":"<div><p>Crohn's disease is a chronic inflammatory bowel disease that affects various intestinal segments and can involve the perianal region. Although anti-tumor necrosis factor (TNF) agents have revolutionized the management of Crohn's disease and improved the prognosis for patients with perianal Crohn's disease (pCD), their long-term effectiveness is limited: over 60% of patients relapse after one year of maintenance therapy. In recent years, significant advances have been made in the treatment of complex perianal fistulas after anti-TNF failure. Concomitant treatment with antibiotics and immunosuppressants improves the effectiveness of anti-TNF agents. Therapeutic drug monitoring and dose adjustment of anti-TNF therapy (targeting a higher trough level) might also improve treatment response. Novel therapeutic strategies might provide new opportunities for pCD management; for example, ustekinumab might be effective after anti-TNF treatment failure, although more studies are needed. As suggested in recent international guidelines, mesenchymal stem cell injection might be an effective, safe treatment for complex pCD.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fd/75/main.PMC8784625.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39879602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of rapid intravenous paracetamol infusion in paediatric patients","authors":"Astrid Eliasen ,&nbsp;Sigrid Otnes ,&nbsp;Merete Matz ,&nbsp;Lise Aunsholt ,&nbsp;René Mathiasen","doi":"10.1016/j.crphar.2021.100077","DOIUrl":"10.1016/j.crphar.2021.100077","url":null,"abstract":"<div><h3>Purpose</h3><p>Paracetamol is recommended as a first-line treatment for pain and fever in paediatric patients. Intravenous (IV) infusions are recommended to be administered as a 15-min infusion to minimize local tissue trauma and related pain. The purpose of this study was to demonstrate that IV paracetamol could be administered during 5 ​min or less in paediatric patients without causing related adverse reactions.</p></div><div><h3>Methods</h3><p>Prospective, observational safety study including children aged &lt;18 years who received IV paracetamol. Pain scores before and after the paracetamol infusions were obtained using VAS, FLACC, COMFORT neo, or COMFORT behaviour scales with scores from 0 to 10 representing no pain to worst pain. Further, objective signs of inflammation at the infusion site were registered.</p></div><div><h3>Findings</h3><p>We included 44 patients (median age 2.8 years, range 0.01–17.0 years) who received paracetamol in a peripheral venous catheter (n ​= ​22) or central venous catheter (n ​= ​22). In total, the 93 paracetamol infusions had a median infusion time of 3:00 ​min, range 0:40 to 5:00 ​min. After infusions, pain scores were lower, compared to before infusions (mean change −0.26, 95% confidence interval −0.45 to −0.07, <em>P</em> ​= ​0.007), and no objective signs of inflammation were reported.</p></div><div><h3>Implications</h3><p>This safety study indicates that IV paracetamol can be administered in paediatric patients with a shorter infusion time than recommended without causing adverse reactions. The results may contribute to a more efficient workflow at paediatric departments.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39891924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal sialylation and fucosylation of saliva glycoproteins: Characteristics of lung cancer-specific biomarkers","authors":"Ziyuan Gao ,&nbsp;Mingming Xu ,&nbsp;Shuang Yue ,&nbsp;Huang Shan ,&nbsp;Jun Xia ,&nbsp;Junhong Jiang ,&nbsp;Shuang Yang","doi":"10.1016/j.crphar.2021.100079","DOIUrl":"10.1016/j.crphar.2021.100079","url":null,"abstract":"<div><p>Dysregulated surface glycoproteins play an important role in tumor cell proliferation and progression. Abnormal glycosylation of these glycoproteins may activate tumor signal transduction and lead to tumor development. The tumor microenvironment alters its molecular composition, some of which regulate protein glycosylation biosynthesis. The glycosylation of saliva proteins in lung cancer patients is different from healthy controls, in which the glycans of cancer patients are highly sialylated and hyperfucosylated. Most studies have shown that O-glycans from cancer are truncated O-glycans, while N-glycans contain fucoses and sialic acids. Because glycosylation analysis is challenging, there are few reports on how glycosylation of saliva proteins is related to the occurrence or progression of lung cancer. In this review, we discussed glycoenzymes involved in protein glycosylation, their changes in tumor microenvironment, potential tumor biomarkers present in body fluids, and abnormal glycosylation of saliva or lung glycoproteins. We further explored the effect of glycosylation changes on tumor signal transduction, and emphasized the role of receptor tyrosine kinases in tumorigenesis and metastasis.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a7/e1/main.PMC8718573.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39891927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simvastatin ameliorates oxidative stress levels in HepG2 cells and hyperlipidemic rats","authors":"Kanika Verma ,&nbsp;Shikha Makwana ,&nbsp;Sarvesh Paliwal ,&nbsp;Vartika Paliwal ,&nbsp;Smita Jain ,&nbsp;Swati Paliwal ,&nbsp;Swapnil Sharma","doi":"10.1016/j.crphar.2022.100088","DOIUrl":"10.1016/j.crphar.2022.100088","url":null,"abstract":"<div><p>Simvastatin is an established anti-hyperlipidemic drug and few studies have indicated its role in the mitigation of oxidative stress. However, a systematic study considering molecular binding/interaction of simvastatin with anti-oxidant enzymes followed by confirmational <em>in vitro</em> and <em>in vivo</em> studies have never been done. We investigated the molecular binding of simvastatin with multiple anti-oxidant enzymes and assessed their levels after the treatment of simvastatin <em>in vitro</em> and <em>in vivo</em>. This study is the first to show the molecular binding of simvastatin to catalase through molecular docking analysis. Moreover, the anti-oxidative properties of simvastatin have not been studied in Lipopolysaccharide (LPS) induced oxidative stress in HepG2 cells. We found that simvastatin effectively attenuated oxidative stress in LPS induced HepG2 cells and high-fat diet (HFD) fed hyperlipidemic rats by increasing the levels of antioxidant enzymes. The activity of catalase and superoxide dismutase (SOD) both increased significantly in oxidatively stressed HepG2 cells after the treatment with simvastatin (10 ​μM, 24 ​h). In addition to this, he original cell morphology of oxidatively stressed cells was restored by simvastatin, and an increase in antioxidant enzymes, catalase (0.08 U/cells to 0.12 U/cells), and SOD (0.57 U/cells to 0.74 U/cells) was also noted in HepG2 cells. Furthermore, a significant increase in the antioxidant enzymes such as Catalase, SOD, and reduced glutathione (GSH) was noted after simvastatin treatment in the HFD model. Moreover, we also observed degradation of by-products of lipid peroxidation thiobarbituric acid reactive substances (TBARs), nitric oxide (NO), and protein carbonyl levels. This indicates that simvastatin enhances anti-oxidant enzyme activities and can be repurposed for the treatment of oxidative stress in liver diseases in humans after extensive clinical trials.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/11/main.PMC8818901.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39908762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacodynamic evaluation of the XOR inhibitor WN1703 in a model of chronic hyperuricemia in rats induced by yeast extract combined with potassium oxonate","authors":"Yuanyuan Li ,&nbsp;Xinying Zhu ,&nbsp;Fuyao Liu,&nbsp;Wen Peng,&nbsp;Lei Zhang,&nbsp;Jing Li","doi":"10.1016/j.crphar.2022.100098","DOIUrl":"10.1016/j.crphar.2022.100098","url":null,"abstract":"<div><p>Hyperuricemia is a common disease caused by a disorder of purine metabolism, which often causes hyperlipidemia and other metabolic diseases. WN1703 was demonstrated to be an effective xanthine oxidoreductase (XOR) inhibitor in our previous study. Here, we evaluated the pharmacodynamic effect of WN1703 on rats suffering from chronic hyperuricemia accompanied by disorders of lipid metabolism. We discovered that WN1703 was an efficacious uric acid (UA)-lowering compound. Simultaneously, it had effect on relieving renal injury, regulating lipid metabolism by reducing levels of triglycerides and low-density lipoprotein-cholesterol, increasing levels of high-density lipoprotein-cholesterol, and improving renal and liver lesions. WN1703 also exhibited anti-inflammatory and antioxidant activity by alleviating the increasing trend of levels of tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1, and malondialdehyde, and improving the activity of superoxide dismutase and glutathione peroxidase. WN1703 appeared to be more effective than febuxostat in inhibiting XOR and had higher antioxidant activity. In general, the pharmacologic action of WN1703 showed a clear dose–effect relationship.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000189/pdfft?md5=7953d7503a72979fce77444ba6a602aa&pid=1-s2.0-S2590257122000189-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45609166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhalation potential of N-Acetylcysteine loaded PLGA nanoparticles for the management of tuberculosis: In vitro lung deposition and efficacy studies","authors":"Vishal Puri ,&nbsp;Kabi Raj Chaudhary ,&nbsp;Arti Singh ,&nbsp;Charan Singh","doi":"10.1016/j.crphar.2022.100084","DOIUrl":"https://doi.org/10.1016/j.crphar.2022.100084","url":null,"abstract":"<div><p>Several studies have stated that mucus is a critical hurdle for drug delivery to the mucosal tissues. As a result, Polymeric nanoparticles that can overcome mucus barriers are gaining popularity for controlled drug delivery into intra-macrophages to attain high intracellular drug concentration. The present study was aimed to fabricate inhalable N-acetylcysteine (NAC) modified PLGA mucus penetrating particles using the double emulsion method (w/o/w) for target delivery to alveolar macrophages and minimize the dose-related adverse effects, efficiently encapsulate hydrophilic drug, sustain the release profile and prolong the retention time for the management of tuberculosis. Among the numerous formulations, the drug/polymer ratio of 1:10 with 0.50% PVA concentration and sonication time for 2 ​min ​s was chosen for further research. The formulated nanoparticles had a mean particle size of 307.50 ​± ​9.54 ​nm, PDI was 0.136 ​± ​0.02, zeta potential about −11.3 ​± ​0.4 ​mV, decent entrapment efficiency (55.46 ​± ​2.40%), drug loading (9.05 ​± ​0.22%), and excellent flowability. FTIR confirmed that NAC and PLGA were compatible with each other. SEM graphs elucidated that the nanoparticles were spherically shaped with a slightly rough surface whereas TEM analysis ensured the nanometer size nanoparticles and coating of lipid over NPs surface. PXRD spectrum concluded the transformation of the drug from crystalline to amorphous state in the formulation. <em>In vitro</em> release pattern was biphasic started with burst release (64.67 ​± ​1.53% within 12hrs) followed by sustained release over 48hrs thus enabling the prolonged replenishing of NAC. <em>In vitro</em> lung deposition study pronounced that coated NAC-PLGA-MPPs showed favorable results in terms of emitted dose (86.67 ​± ​2.52%), MMAD value (2.57 ​± ​0.12 ​μm), GSD value (1.55 ​± ​0.11 ​μm), and FPF of 62.67 ​± ​2.08% for the deposition and targeting the lungs. Finally, <em>in vitro</em> efficacy studies demonstrated that NAC-PLGA-MPPs presented more prominent antibacterial activity against <em>MTB</em> H37Rv strain as compared to NAC. Hence, PLGA based particles could be a better strategy to deliver the NAC for lung targeting.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000049/pdfft?md5=9d6ce61748d75bd93ac5b28f8736af54&pid=1-s2.0-S2590257122000049-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91588968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Down regulation of fatty acid synthase via inhibition of PI3K/AKT/mTOR in ovarian cancer cell line by novel organoselenium pseudopeptide","authors":"Abeer M. El-Saudi ,&nbsp;Miram A. Altouhamy ,&nbsp;Saad Shaaban ,&nbsp;Farid A. Badria ,&nbsp;Magdy M. Youssef ,&nbsp;Fardous F. El-Senduny","doi":"10.1016/j.crphar.2022.100134","DOIUrl":"10.1016/j.crphar.2022.100134","url":null,"abstract":"<div><p>Ovarian cancer (OC) is the 7th most common cancer in women world-wide and the 3rd most common female cancer. For the treatment of OC, there is no successful therapeutic. The medications that are currently available have significant side effects and a low therapeutic index. This work aimed to evaluate the anticancer activity of organoselenium pseudopeptide compound against OC cell lines. After treatment with 50 ​μM of compound <strong>4</strong> (CPD <strong>4</strong>), the viability was determined. The anticancer activity was further investigated by different methods including cell cycle and apoptosis analysis, colony formation assay, zymography, comet assay and Western blot. In comparison to a positive control, compound <strong>4</strong> showed cytotoxicity toward A2780CP cells rather than A2780 and SKOV-3 ​cells. Compound <strong>4</strong> was more selective to OC cells rather than HSF cells. Moreover, Compound <strong>4</strong> was able to inhibit cell migration and proliferation. The anticancer effect of compound <strong>4</strong> was found to be partially <em>via</em> cell cycle arrest, overexpression of p27 ​cell cycle inhibitor and induction of apoptosis through DNA fragmentation and activated production of ROS. Compound <strong>4</strong> had a differential effect on the modulation of PI3K/AKT/mTOR signaling pathway in the OC treated cell lines, also inhibited lipogenesis process <em>via</em> downregulation of FASN expression. <strong>Conclusion</strong>: This work highlights the unique role of Compound <strong>4</strong> against OC <em>via</em> modulation of oxidative stress, inhibition of survival PI3K/AKT/mTOR pathway. Compound <strong>4</strong> was found to be a promising alternative therapy for the treatment of OC in this investigation.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100134"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/3b/main.PMC9780069.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10438049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amelioration of experimentally induced inflammatory arthritis by intra-articular injection of visnagin","authors":"Sowmyasree Gurram,&nbsp;Pratibha Anchi,&nbsp;Biswajit Panda,&nbsp;Sayali Santosh Tekalkar,&nbsp;Ravindra Bapu Mahajan,&nbsp;Chandraiah Godugu","doi":"10.1016/j.crphar.2022.100114","DOIUrl":"10.1016/j.crphar.2022.100114","url":null,"abstract":"<div><h3>Background</h3><p>Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia, cartilage destruction and bone erosion. Visnagin (VIS) is a proven anti-inflammatory agent and in this study, we aimed to evaluate the anti-arthritic activity of VIS when administered via intra-articular (I.A.) route of administration.</p></div><div><h3>Materials and methods</h3><p>RAW 264.7 ​cells were stimulated with lipopolysaccharide (LPS) (1 ​μg/mL) and treated with VIS at concentrations of 12.5 and 25 ​μM. Arthritis was induced in Sprague Dawley rats by administering Complete Freund's Adjuvant (CFA) (1 ​mg/mL) through (I.A.) route and treated with VIS via (I.A.) route at doses of 3 and 10 ​mg/kg twice a week for 3 weeks. Protective effects were assessed by arthritic score, behavioral studies for pain evaluation, radiological assessment, histopathological examination and molecular studies.</p></div><div><h3>Results</h3><p>Our results indicated that VIS significantly reduced LPS induced inflammation in RAW 264.7 ​cells. While in arthritic rats, VIS reduced the disease scorings with improvement towards pain. Pathological examination demonstrated that VIS reduced knee joint inflammation and cartilage destruction. Radiographic analysis and molecular studies also supported the protective effects of VIS.</p></div><div><h3>Conclusion</h3><p>The results of the study imply that VIS exerted potential anti-inflammatory and anti-arthritic activity in <em>in vitro</em> and <em>in vivo</em> models of RA.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/ef/main.PMC9389203.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of fenfluramine for the treatment of Dravet syndrome patients","authors":"Kayla Simon ,&nbsp;Hunter Sheckley ,&nbsp;Christopher L. Anderson ,&nbsp;Zhao Liu ,&nbsp;Paul R. Carney","doi":"10.1016/j.crphar.2021.100078","DOIUrl":"10.1016/j.crphar.2021.100078","url":null,"abstract":"<div><h3>Introduction</h3><p>Dravet Syndrome (DS) is a rare epileptiform disorder typically presenting within the first year of life of a normally developing infant. It is characterized by several prolonged seizures that are often resistant to current anti-epileptic drug (AED) regimens. This paper outlines the history and clinical trials of the drug fenfluramine, a drug that when used in addition to AED regimens may provide hope to children affected by DS.</p></div><div><h3>Body</h3><p>Fenfluramine (3-trifulormethyl-N-ethylamphetamine) is an amphetamine derivative that primarily affects serotonin neurotransmitter levels. It was initially prescribed in the 1960s as an appetite suppressant marketed as a weight loss drug. However, it was removed from the markets due to its association with cardiac valvopathies. It continued to by studied in epilepsy by Gastaut in the 1980s in children with self-induced syncope and irretractable epilepsy. In 2012, Ceulemans et al. studied the use of fenfluramine in patients with DS. Following the success of that retrospective case study, Nabbout et al. and Legae et al. conducted two randomized control trials leading to the FDA approval of fenfluramine under its trade name Fintepla in 2020.</p></div><div><h3>Discussion</h3><p>The success of the randomized control trials suggests the addition of fenfluramine to current AED regimens may lead to better control of seizures in patients with DS. The side effects of fenfluramine prove to be manageable and the concern for valvopathies has not been reproducible with low dose fenfluramine.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3b/61/main.PMC8695265.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}