Fundamental & Clinical Pharmacology最新文献

{"title":"Effect of a Single Oral Dose of Dexamphetamine or Zolpidem on Attention and Reaction Time in Healthy Men.","authors":"Veronika Pfoser-Poschacher, Michael Wolf, Michaela Bayerle-Eder, Teresa Wimmer, Daniela Boryshchuk, Christopher Gerner, Michael Wolzt","doi":"10.1111/fcp.70092","DOIUrl":"10.1111/fcp.70092","url":null,"abstract":"<p><p>Psychotropic medicines are known to impair cognitive function acutely, but the specific effects of individual substances remain underexplored. This study investigates the effects of dexamphetamine and zolpidem on cognitive performance to quantify the potential risk of intake and their pharmacokinetic and pharmacodynamic relationship. This randomized, double-blind, placebo-controlled trial (EudraCT 2021-005381 - 17) included 60 healthy men aged 26 ± 5 (mean ± SD) years. Participants received a single oral dose of 30-mg dexamphetamine, 5-mg zolpidem, or placebo (n = 20 per group). Cognitive performance was assessed at baseline and 3 and 8 h after dosing using the computerized Psytest system. Dexamphetamine and zolpidem improved sustained attention, with significant reduction of omissions at 8 h. Reaction time improved in both groups, but zolpidem impaired phasic alertness. Working memory remained unchanged. Plasma concentration of dexamphetamine and zolpidem was 70.8 ± 10.4 ng/mL and 39.0 ± 20.7 ng/mL at 3 h and 45.9 ± 7.9 ng/mL and 8.7 ± 6.6 ng/mL at 8 h, respectively. No correlation between drug plasma concentration and cognitive performance measures was demonstrable. Dexamphetamine caused the strongest subjective effects and highest liking ratings, whereas zolpidem elicited greater subjective dislike. Tolerability was best with placebo, followed by zolpidem and dexamphetamine. Single therapeutic doses of dexamphetamine and zolpidem modestly affected cognitive function 3 h after intake, with no relationship between cognitive performance and the study medicines' plasma concentration. Both medicines improve cognition after 8 h but differed in subjective emotional effects. Nevertheless, generalizability is limited by the inclusion of healthy men only. Trial Registration: EudraCT: Nr: 2021-005381-17.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":"e70092"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836951","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148089252","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148088194","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148088193","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148084974","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148080758","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":"Preventive Effects of trans-4-Methoxy-β-nitrostyrene on Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats","authors":"Matyelle Jussára Rodrigues-Silva,&nbsp;Rodrigo José Bezerra de Siqueira,&nbsp;Karoline Gonzaga-Costa,&nbsp;Yeimer Antonio Santiago Guevara,&nbsp;Marcus Lins Queiroga,&nbsp;Davi Benevides Almeida,&nbsp;Alexandre Havt,&nbsp;Renata Fereirra Carvalho Leitão,&nbsp;Liova Chabot Díaz,&nbsp;Ana Paula Negreiros Nunes Alves,&nbsp;Glória Pinto Duarte,&nbsp;Rosivaldo Santos Borges,&nbsp;Armênio Aguiar dos Santos,&nbsp;Pedro Jorge Caldas Magalhães,&nbsp;Saad Lahlou","doi":"10.1111/fcp.70078","DOIUrl":"10.1111/fcp.70078","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The soluble guanylate cyclase (sGC)/GMPc pathway plays an important in pulmonary arterial hypertension (PAH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We investigated whether <i>trans</i>-4-methoxy-β-nitrostyrene (T4MN), a novel sGC stimulator, prevents development of monocrotaline (MCT)-induced HAP in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>At Day 0 (D0), rats were injected with MCT (60 mg/kg, sc). Control (CNT) rats received an equal volume of MCT vehicle only. MCT-injected rats were divided into four groups, which were treated orally once a day from D1 to D28 with one of the following: T4MN vehicle (MCT-V group), T4MN at 18.75 mg/kg (MCT-T4MN1 group), T4MN at 37.50 mg/kg (MCT-T4MN2 group), or sildenafil (SIL; 10 mg/kg) (MCT-SIL group).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to the CNT group, MCT treatment induced a significant increase in heart weight to body weight, lung weight to body weight, and right ventricular systolic pressure but significantly reduced the maximum vasorelaxation (Rmax) induced by acetylcholine in aortic ring preparations. Indeed, MCT treatment increased the wall thickness of small pulmonary arterioles and reduced the mRNA levels of BMPR2, eNOS, and VEGF-A while it increased that of IL-6 in pulmonary tissue. All these effects of MCT, except those on mRNA expression levels in the lungs, were significantly reduced by preventive treatment with T4MN or SIL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, the present study provided the first evidence that T4MN prevents the development of MCT-induced HAP in rats. Further mechanistic studies of these protective effects of T4MN are warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511526","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":"Factors Associated With Cocaine Use Disorder: Results From the French Nationwide Repeated Cross-Sectional OPPIDUM Study (2019–2023)","authors":"Zenab Alhamidi,&nbsp;Clémence Lacroix,&nbsp;Elisabeth Jouve,&nbsp;Thomas Soeiro,&nbsp;Céline Eiden,&nbsp;Joëlle Micallef","doi":"10.1111/fcp.70081","DOIUrl":"10.1111/fcp.70081","url":null,"abstract":"<p>Cocaine use has increased both globally and nationally. This trend is accompanied by a rise in clinical complications. The objective of our study was to identify factors observed to be associated with cocaine use disorder, using data from the OPPIDUM program, collecting information directly from patients with substance use disorders recruiting in care or harm reduction facilities. Cocaine users were divided into two groups: cocaine use disorder and simple use. A univariate analysis was performed to compare the groups, followed by a multivariate analysis to identify factors associated with cocaine use disorder. Between 2019 and 2023, 6863 cocaine users (28% of all OPPIDUM participants) from 116 addiction treatment centers were included. Several factors were found to be significantly associated with cocaine use disorder: extreme precariousness (OR = 1.34, 95% CI [1.12–1.61], <i>p</i> = 0.002), cocaine-only use (OR = 1.90, 95% CI [1.45–2.50], <i>p</i> &lt; 0.0001), alcohol dependence (OR = 1.48, 95% CI [1.30–1.68], p &lt; 0.0001), and use of antidepressants and antipsychotics (OR = 2.08, 95% CI [1.37–3.16], <i>p</i> = 0.001; OR = 1.94, 95% CI [1.40–2.69], <i>p</i> &lt; 0.001). These findings highlight several key factors associated with cocaine use disorder and their clinical implications. The study has limitations: potential selection bias, repeated inclusion of the same users across years, multiple modes of cocaine use, and the exploratory nature of the analyses due to uncontrolled alpha risk. Nevertheless, these insights can help healthcare professionals better understand patient profiles and provide more tailored care and prevention strategies.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511558","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":"Targeting Neuroinflammation in Alzheimer's Disease: Repurposed Nucleoside Reverse Transcriptase Inhibitors and the Therapeutic Potential of Kamuvudine-9","authors":"Mariyam Hussain,&nbsp;Mohammad Ikram,&nbsp;Divya Vohora","doi":"10.1111/fcp.70079","DOIUrl":"10.1111/fcp.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a progressive neurological illness that causes cognitive deterioration. Current medications only help with the symptoms to a limited extent. Over the past decade, nucleoside reverse transcriptase inhibitors (NRTIs), historically used as antiretrovirals, have appeared as surprising contenders for modifying <span>AD</span>. Aside from their antiviral activity, NRTIs have immunomodulatory actions, such as inhibiting the NLRP3 inflammasome, lowering amyloid and tau pathology and modulating neuroinflammation. A second-generation analogue, Kamuvudine-9, has been designed to balance these neuroprotective advantages with reduced mitochondrial toxicity and off-target antiviral effects, offering a safer long-term solution for chronic neurodegenerative disorders. This review synthesises mechanistic data, preclinical data, observational studies and new clinical findings to make a unified case for NRTIs and K-9 as multitarget therapeutic compounds in <span>AD</span>. By emphasising their dual mechanism, retroelement inhibition and inflammasome blockade coupled with innovation in drug delivery and pharmacogenomics, we highlight how repurposing this class would remake the therapeutic landscape. In contrast to amyloid-directed interventions, NRTIs and K-9 act on converging inflammatory and genetic mechanisms that mediate both amyloid and tau pathology, making them universal modulators of disease course. Prospects for future advances in precision medicine, nanocarrier delivery and large-scale validation of interventions may reveal a new generation of accessible, disease-modifying treatments for <span>AD</span>.</p>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511602","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":"RETRACTION: Vitamin D3 Potentiates the Nephroprotective Effects of Vildagliptin–Metformin Combination in a Rat Model of Metabolic Syndrome","authors":"","doi":"10.1111/fcp.70080","DOIUrl":"10.1111/fcp.70080","url":null,"abstract":"<p>\u0000 <b>RETRACTION</b>: <span>N. S. Wahba</span>, <span>R. H. Abdel-Ghany</span>, <span>S. A. Ghareib</span>, <span>M. Abdel-Aal</span>, <span>A. E. Alsemeh</span>, and <span>D. Sabry</span>, “ <span>Vitamin D3 Potentiates the Nephroprotective Effects of Vildagliptin–Metformin Combination in a Rat Model of Metabolic Syndrome</span>,” <i>Fundamental &amp; Clinical Pharmacology</i> <span>36</span>, no. <span>2</span> (<span>2022</span>): <span>306</span>–<span>323</span>, https://doi.org/10.1111/fcp.12721.\u0000 </p><p>The above article, published online on 28 August 2021 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Luc Zimmer; the Société Française de Pharmacologie et de Thérapeutique; and John Wiley &amp; Sons Ltd. The retraction has been agreed upon following concerns raised by a third-party regarding data overlaps between this article and two other articles published elsewhere by the same authors. Following investigation, the editors confirmed that there are substantial overlaps between the three papers. The authors provided numerical data but were unable to provide any raw data due to the time that has elapsed since publication. They explained that the three studies were closely related, and that the two overlapping articles were cited in their paper. However, this explanation does not account for the overlaps of data between different treatments and groups across the three articles. Given the extent of the issues identified, the editors have lost confidence in the data presented and consider the conclusions unreliable. The authors disagree with the retraction.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511532","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}