Fundamental & Clinical Pharmacology最新文献

{"title":"Alterations in the gene expression of SARS-COV-2 entry receptors and enzymes in lungs and hearts of controlled and uncontrolled diabetic mice","authors":"Ohood Alkhawaldeh, Yazun Jarrar, Munir Gharaibeh, Sara Abudahab, Dina Abulebdah, Bashir Jarrar","doi":"10.1111/fcp.12964","DOIUrl":"10.1111/fcp.12964","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell is carried out by specific receptors and enzymes, including human angiotensin-converting enzyme 2 receptor (ACE2), transmembrane serine protease 2 (TMPRSS2), and cathepsin-L (CTSL). COVID-19 patients with comorbidities, such as diabetes mellitus (DM), are more prone to severe symptoms and have a higher risk of mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The present study aimed to investigate the impact of controlled and uncontrolled type 1 DM (T1DM) on the gene expression of mouse <i>Ace2</i>, <i>Tmprss2</i>, and <i>Ctsl</i> and correlate it with the pathological alterations in the lungs and the heart of DM mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Balb/c mice were administered a single dose of 240 mg/kg streptozocin to induce T1DM. The blood glucose level was measured to confirm the induction of DM. Normalization of blood glucose levels in T1DM mice was achieved using 0.1 mL/kg Mixtard® insulin therapy. The mice's lungs and hearts were harvested, and the mRNA was extracted and converted to cDNA. The gene expression of <i>Ace2</i>, <i>Tmprss2</i>, <i>Ctsl</i>, <i>Cyp4a11</i>, and <i>Adrb1</i> genes, which play a role in the homeostasis of lungs and hearts, were measured using quantitative real-time polymerase chain reaction (RT-PCR). The pathological alterations in the hearts and lungs induced by T1DM were evaluated using the relative heart and lung weights, in addition to the pathohistological examination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After inducing T1DM for 14 days, we observed a significant reduction in the total weight of uncontrolled DM (UDM) mice (<i>P</i> < 0.05). Pathohistological examination of UDM lung tissues revealed thickening of the alveolar walls with narrowing of the surface of the alveolar sacs. Additionally, we found that UDM mice exhibited downregulation of <i>Ace2</i> gene expression (<i>P</i> < 0.05) in their lungs, while both UDM and control DM (CDM) mice showed upregulation of <i>Ctsl</i> gene expression in their hearts (<i>P</i> < 0.05). Notably, <i>Cyp4a12</i> gene expression was significantly downregulated (<i>P</i> < 0.05) in UDM mice but returned to normal levels in CDM mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We conclude from this study that T1DM downregulates <i>Ace2</i> receptor and <i>Cyp4a12</i> gene expression, which is correlated with the thickening of alveolar walls and narrowing of the surface of alveolar sacs in the ","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 2","pages":"328-340"},"PeriodicalIF":2.9,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72209122","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":"Cardiac and hepatic side effects of fluoxetine in male and female adolescent rats","authors":"Hajar Babaaeyan,&nbsp;Nona Sakhaie,&nbsp;Farshid Sadegzadeh,&nbsp;Hakimeh Saadati,&nbsp;Ali Niapour","doi":"10.1111/fcp.12963","DOIUrl":"10.1111/fcp.12963","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fluoxetine (FLX) is widely prescribed as an antidepressant medicine in the juvenile population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Although some adverse effects of FLX have been reported in adults, the present study aimed to investigate the side effects of FLX treatment during adolescence on the cardiac and hepatic systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male and female rats were gavaged with FLX (5 mg/kg/day) on postnatal days (PND) 21 to PND 60. Following treatment, blood samples were collected and hepatic enzymes were evaluated. The specimens of the liver and heart of animals were subjected to histopathological assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fluoxetine significantly raised serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in males, whereas the aspartate aminotransferase (AST) level increased in both male and female animals. In the histopathological study, hepatic plates were more seriously affected, and the sinusoids were irregular in adolescent male rats. Degenerative changes were observed especially in the first and second hepatic zones of FLX-treated male rats. Signs of inflammation and accumulation of lymphoid groups were frequently observed in the portal triad of the hepatic lobules. These alterations were more severe in male livers. Minimum or nearly normal changes were observed in female liver slides. In addition, the histological assessment indicated that treatment with FLX during adolescence also increased the heart's weight and the wall thickness of the right and left ventricles (hypertrophy) in male and especially female animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings may provide new insights into the cardiac and hepatic adverse effects of FLX.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 2","pages":"320-327"},"PeriodicalIF":2.9,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480701","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":"Analgesic switching in chronic users of dextropropoxyphene in France","authors":"Amélie Daveluy,&nbsp;Michael Charles Bryan,&nbsp;Ghada Miremont-Salamé,&nbsp;Régis Lassalle,&nbsp;Clémentine Lacueille,&nbsp;Angela Grelaud,&nbsp;Marie Floccia,&nbsp;Françoise Haramburu,&nbsp;Maryse Lapeyre-Mestre,&nbsp;Joëlle Micallef,&nbsp;Francesco Salvo","doi":"10.1111/fcp.12962","DOIUrl":"10.1111/fcp.12962","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The combination dextropropoxyphene/paracetamol (DXP/P) was the most prescribed opioid analgesic until its withdrawal in 2011.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study investigated dispensations of analgesics in chronic users of DXP/P during the 18 months following its withdrawal.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional study repeated yearly was conducted by using the French reimbursement database from 2006 to 2015. Chronic DXP/P users were defined as patients who received at least 40 boxes of DXP/P in the year prior to withdrawal. Data on analgesic dispensing were analyzed at DXP/P withdrawal (T0) and then every 6 months for 18 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 63 671 subjects had a DXP/P reimbursement in the year prior to its discontinuation, of whom 7.1% were identified as chronic users (mean age: 71.5 years, women: 68.7%). Among the patients taking DXP/P alone at T0 (74.6%), one fourth switched to a peripheral analgesic, one fourth to a combination of peripheral analgesic/opioid, one fourth to another opioid, and the others mainly discontinued their treatment (14.1%) or died. During the following 12 months, most of the subjects taking only peripheral analgesics continued this treatment, while half of the subjects with a combination of opioid/peripheral analgesic or taking only an analgesic remained on this type of treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Eighteen months after DXP/P withdrawal, more than 10% of patients stopped taking an analgesic. Vigilance is required regarding any change in analgesics by regularly reassessing patients' pain and, in the case of opioid treatments, by monitoring the risk of use disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 2","pages":"389-397"},"PeriodicalIF":2.9,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.12962","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49676710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epothilone B loaded in acellular nerve allograft enhanced sciatic nerve regeneration in rats","authors":"Zhikal Omar Khudhur,&nbsp;Shang Ziyad Abdulqadir,&nbsp;Abdullah Faqiyazdin Ahmed Mzury,&nbsp;Abdulrahman Aziz Rasoul,&nbsp;Shukur Wasman Smail,&nbsp;Mohammad B. Ghayour,&nbsp;Arash Abdolmaleki","doi":"10.1111/fcp.12961","DOIUrl":"10.1111/fcp.12961","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Epothilone B (EpoB) is a microtubule-stabilizing agent with neuroprotective properties.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study examines the regenerative properties of ANA supplemented with EpoB on a sciatic nerve deficit in male Wistar rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For this purpose, the 10 mm nerve gap was filled with acellular nerve allografts (ANAs) containing EpoB at 0.1, 1, and 10 nM concentrations. The sensorimotor recovery was evaluated up to 16 weeks after the operation. Real-time PCR, histomorphometry analysis, and electrophysiological evaluation were also used to evaluate the process of nerve regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ANA/EpoB (0.1 nM) significantly improved sensorimotor recovery in rats compared to ANA, ANA/EpoB (1 nM), and ANA/EpoB (10 nM) groups. This led to reduced muscle atrophy, improved sciatic functional index, and thermal paw withdrawal reflex latency, indicating nerve regeneration and target organ reinnervation. The electrophysiological and histomorphometry findings also confirmed the ANA/EpoB regenerative properties (0.1 nM). EpoB only enhanced ANA regenerative properties at 0.1 nM, with no therapeutic effects at higher concentrations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Totally, we concluded that ANA loaded with 0.1 nM EpoB can effectively reconstruct the transected sciatic nerve in rats, likely by enhancing axonal sprouting and extension.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 2","pages":"307-319"},"PeriodicalIF":2.9,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49676711","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":"Synthesis, molecular docking, ADMET, and evaluation of the anxiolytic effect in adult zebrafish of synthetic chalcone (E)-3-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one: An in vivo and in silico approach","authors":"Larissa Santos Oliveira,&nbsp;Maria Kueirislene Amâncio Ferreira,&nbsp;Francisco Wagner de Queiroz Almeida-Neto,&nbsp;Antonio Wlisses da Silva,&nbsp;José Ivo Lima Pinto Filho,&nbsp;Matheus Nunes da Rocha,&nbsp;Emanuelle Machado Marinho,&nbsp;Walber Henrique Ferreira Ribeiro,&nbsp;Márcia Machado Marinho,&nbsp;Emmanuel Silva Marinho,&nbsp;Jane Eire Silva Alencar de Menezes,&nbsp;Hélcio Silva dos Santos","doi":"10.1111/fcp.12960","DOIUrl":"10.1111/fcp.12960","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anxiety disorders represent the complex interaction between biological, psychological, temperamental, and environmental factors; drugs available to treat anxiety such as benzodiazepines (BZDs) are associated with several unwanted side effects. Although there are useful treatments, there is still a need for more effective anxiolytics with better safety profiles than BZDs. Chalcones or 1,3-diphenyl-2-proper-1-ones can be an alternative since this class of compounds has shown therapeutic potential mainly due to interactions with GABA_A receptors and serotonergic system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study evaluated the anxiolytic potential of chalcone (<i>E</i>)-3-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (C2OHPDA) in adult zebrafish (<i>Danio rerio</i>) (ZFa).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Each animal (<i>n</i> = 6/group) was treated intraperitoneally (i.p.; 20 μL) with the chalcone (4, 20, and 40 mg/kg) and with the vehicle (DMSO 3%; 20 μL), being submitted to the tests of locomotor activity and 96-h acute toxicity. The light/dark test was also performed, and the serotonergic mechanism (5-HT) was evaluated through the antagonists of the 5-HTR₁, 5-HTR_2A/2C, and 5-HTR_3A/3B receptors. It was investigated the prediction of the chalcone's position and preferential orientation concerning its receptor, as well as the pharmacokinetic parameters (ADMET) involved in the process after administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>As a result, C2OHPDA was not toxic and reduced the locomotor activity of ZFa. Furthermore, chalcone demonstrated an anxiolytic effect on the central nervous system (CNS), mediated by the serotonergic system, with action on 5-HT_2A and 5-HTR_3A/3B receptors. The interaction of C2OHPDA with 5-HT_2AR and 5-HT_3A receptors was confirmed by molecular docking study, the affinity energy observed was −8.7 and −9.1 kcal/mol, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Thus, this study adds new evidence and highlights that chalcone can potentially be used to develop compounds with anxiolytic properties.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 2","pages":"290-306"},"PeriodicalIF":2.9,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41234578","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 signals of myopathy associated with statin and contraindicated comedications in the realworld","authors":"Sewon Park,&nbsp;Ju Won Lee,&nbsp;Dal Ri Nam,&nbsp;Sun-Young Jung","doi":"10.1111/fcp.12959","DOIUrl":"10.1111/fcp.12959","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Using statins in combination with other drugs was reported to increase the risk of myopathy. However, there was a sparse number of studies on the incidence of adverse events (AEs) associated with the concomitant use of statin and contraindicated drugs in the real world.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to identify the risk of concomitant use of statins with contraindicated drugs by exploring signals related to statin–drug interactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a disproportionality analysis for drugs and AEs by applying the case/non-case study using the KIDS-KAERS database (KIDS-KD), 2016–2020. A case was defined as an individual case safety reports (ICSRs) including “rhabdomyolysis/myopathy.” A non-case was defined as an ICSR, including all other AEs. We applied Ω shrinkage measure model, chi-square statics model, additive model, multiplicative model, and combination risk ratio model to detect signals of myopathy due to statin with concomitant drugs including antiviral agents, immunosuppressants, and antifungals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1 011 234 ICSRs, 2708 were cases, with 861 cases of statin monotherapy and 1248 of concomitant uses of statin. The adjusted reporting odds ratios were 3.27 (95% confidence interval [CI]: 3.11–3.43), 8.70 (95% CI: 8.04–9.40), and 1.83 (95% CI: 1.73–1.94), respectively. Several combinations of signals were detected through an additive model or multiplicative model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Signals of an increased risk of myopathy associated with the use of statins with concomitant drugs, including contraindicated drugs, were confirmed in a real-world setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 2","pages":"380-388"},"PeriodicalIF":2.9,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41198795","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":"Breast cancer resistance protein polymorphism ABCG2 c.421C>A (rs2231142) moderates the effect of valproate on lamotrigine trough concentrations in adults with epilepsy","authors":"Ivana Šušak Sporiš,&nbsp;Nada Božina,&nbsp;Iva Klarica Domjanović,&nbsp;Davor Sporiš,&nbsp;Silvio Bašić,&nbsp;Ivana Bašić,&nbsp;Mila Lovrić,&nbsp;Lana Ganoci,&nbsp;Vladimir Trkulja","doi":"10.1111/fcp.12958","DOIUrl":"10.1111/fcp.12958","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Valproate inhibits clearance of lamotrigine and greatly increases its concentrations. We assessed whether this effect was moderated by a polymorphism (<i>ABCG2 c.421C&gt;A</i>) of the breast cancer resistance protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In two consecutive independent studies in adults with epilepsy on lamotrigine monotherapy or cotreated with valproate: (i) Exposure to valproate was considered treatment, (ii) dose-adjusted lamotrigine troughs at steady state were the outcome, and (iii) <i>ABCG2 c.421C&gt;A</i> genotype (wild-type [wt] homozygosity or variant carriage) was the tested moderator. We used entropy balancing (primary analysis) and exact/optimal full matching (secondary analysis) to control for confounding, including polymorphisms (and linked polymorphisms) suggested to affect exposure to lamotrigine (<i>UGT1A4*3 c.142T&gt;G</i>, rs2011425; <i>UGT2B7–161C&gt;T</i>, rs7668258; <i>ABCB1 1236C&gt;T</i>, rs1128503) to generate frequentist and Bayesian estimates of valproate effects (geometric means ratios [GMR]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The two studies yielded consistent results (replicated); hence, we analyzed combined data (total <i>N</i> = 471, 140 treated, 331 controls, 378 <i>ABCG2 c.421C&gt;A</i> wt subjects, 93 variant carriers). Primary analysis: in variant carriers, valproate effect (GMR) on lamotrigine (treated, <i>n</i> = 21 vs. controls, <i>n</i> = 72) was around 60% higher than in wt subjects (treated, <i>n</i> = 119 vs. controls, <i>n</i> = 259)—ratio of GMRs 1.61 (95%CI 1.23–2.11) (frequentist) and 1.63 (95%CrI 1.26–2.10) (Bayes). Similar differences in valproate effects between variant carriers and wt subjects were found in the secondary analysis (valproate troughs up to 364 μmol/L vs. no valproate; or valproate ≥364 μmol/L vs. no valproate). Susceptibility of the estimates to unmeasured confounding was low.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Data suggest that polymorphism rs2231142 moderates the effect of valproate on exposure to lamotrigine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 2","pages":"351-368"},"PeriodicalIF":2.9,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41108242","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":"Neuroprotective effects of riluzole in Alzheimer's disease: A comprehensive review","authors":"Maryam Golmohammadi,&nbsp;Mohammadreza Mahmoudian,&nbsp;Ekhlas Khammas Hasan,&nbsp;Shadia Hamoud Alshahrani,&nbsp;Rosario Mireya Romero-Parra,&nbsp;Jitendra Malviya,&nbsp;Ahmed Hjazi,&nbsp;Mazin A. A. Najm,&nbsp;Abbas F. Almulla,&nbsp;Mohammad Yasin Zamanian,&nbsp;Mona Kadkhodaei,&nbsp;Nazanin Mousavi","doi":"10.1111/fcp.12955","DOIUrl":"10.1111/fcp.12955","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite several hundred clinical trials of drugs that initially showed promise, there has been limited clinical improvement in Alzheimer's disease (AD). This may be attributed to the existence of at least 25 abnormal cellular pathways that underlie the disease. It is improbable for a single drug to address all or most of these pathways, thus even drugs that show promise when administered alone are unlikely to produce significant results. According to previous studies, eight drugs, namely, dantrolene, erythropoietin, lithium, memantine, minocycline, piracetam, riluzole, and silymarin, have been found to target multiple pathways that are involved in the development of AD. Among these drugs, riluzole is currently indicated for the treatment of medical conditions in both adult patients and children and has gained increased attention from scientists due to its potential in the excitotoxic hypothesis of neurodegenerative diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to investigate the effects of drugs on AD based on cellular and molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The literature search for this study utilized the Scopus, ScienceDirect, PubMed, and Google Scholar databases to identify relevant articles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Riluzole exerts its effects in AD through diverse pathways including the inhibition of voltage-dependent sodium and calcium channels, blocking AMPA and NMDA receptors and inhibiting the release of glutamic acid release and stimulation of EAAT1-EAAT2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this review article, we aimed to review the neuroprotective properties of riluzole, a glutamate modulator, in AD, which could benefit patients with the disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 2","pages":"225-237"},"PeriodicalIF":2.9,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123967","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":"Evaluation of anti-inflammatory activity of kaurenol: Experimental evaluation and mechanistic insights","authors":"Ricardo Andrade Furtado,&nbsp;Samir A. Ross,&nbsp;Silvio de Almeida Junior,&nbsp;Rafael Paranhos de Mendonça,&nbsp;Cristiane Teixeira Vilhena Bernardes,&nbsp;Mauro Nogueira da Silva,&nbsp;Karina Furlani Zoccal,&nbsp;Lúcia Helena Faccioli,&nbsp;Jairo Kenupp Bastos","doi":"10.1111/fcp.12957","DOIUrl":"10.1111/fcp.12957","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Kaurenol, a diterpene alcohol found in Copaifera langsdorffii Desf. (known as “copaiba”), is historically used in traditional medicine for inflammatory conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aims to comprehensively assess the potential anti-inflammatory and antinociceptive properties of kaurenol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To this end, the following experiments were conducted to evaluated toxicity: locomotor performance and acute toxicity; nociception: acetic acid-induced writhing and formalin-induced antinociception; and anti-inflammatory activity: carrageenan and dextran-induced paw edema at 10, 20, and 40 mg/kg, and measurement of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in macrophages at 1, 3, and 9 μg/ml.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Kaurenol did not show significant locomotor changes, acute toxicity, and central analgesic activity in the first phase of formalin test at dosages tested. Kaurenol showed 53%, 64%, 64%, and 58% of inhibition in the acetic acid-induced writhing, second phase of formalin test, carrageenan and dextran-induced paw edema, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The anti-inflammatory activity was associated with the regulation of NO release and probably with the regulation of mediators, such as serotonin and prostaglandin in vascular permeability, as well as by being associated with the regulation of IL-6 and IL-10. Kaurenol display anti-inflammatory activity but has no analgesic activity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 2","pages":"252-261"},"PeriodicalIF":2.9,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41120405","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":"Changes in serotonin neurotransmission as assayed by microdialysis after acute, intermittent or chronic ethanol administration and withdrawal","authors":"Abdelkader Dahchour,&nbsp;Roberta J. Ward","doi":"10.1111/fcp.12949","DOIUrl":"10.1111/fcp.12949","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The serotonergic neurotransmitter system is involved in many ethanol-induced changes, including many behavioural alterations, as well as contributing to alcohol dependence and its withdrawal.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review has evaluated microdialysis studies where alterations in the serotonin system, that is, serotonin, 5-HT, or its metabolite 5-hydroxyindoleacetic acid, 5-HIAA, have been reported during different ethanol intoxication states, as well as in animals showing alcohol preference or not. Changes in 5-HT receptors and the 5-HT transporter are briefly reviewed to comprehend the significance of changes in microdialysate 5-HT concentrations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>Changes in 5-HT content following acute, chronic and during ethanol withdrawal states are evaluated. In addition, the serotoninergic system was assessed in animals that have been genetically selected for alcohol preference to ascertain whether changes in this monoamine microdialysate content may contribute to alcohol preference.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and discussion</h3>\u0000 \u0000 <p>Changes occurred in 5-HT signalling in the limbic brain regions, increasing after acute ethanol administration in specific brain regions, particularly at higher doses, while chronic alcohol exposure essentially decreased serotonergic transmission. Such changes may play a pivotal role in emotion-driven craving and relapse. Depending on the dosage, mode of administration and consumption rate, ethanol affects specific brain regions in different ways, enhancing or reducing 5-HT microdialysate content, thereby inducing behavioural and cognitive functions and enhancing ethanol consumption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Microdialysis studies demonstrated that ethanol induces several alterations in 5-HT content as well as its metabolites, 5-HIAA and 5-HTOL, not only in its release from a specific brain region but also in the modifications of its different receptor subtypes and its transporter.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 1","pages":"42-59"},"PeriodicalIF":2.9,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243770","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}