Fundamental & Clinical Pharmacology最新文献

This review highlights the integration of drug repurposing and nanotechnology-driven delivery strategies as innovative approaches to enhance the antifungal activity of statins against mucosal candidiasis, providing a framework for future translational research and clinical application. The rising prevalence of antifungal resistance and virulence factors of Candida albicans underscore the limitations of current therapies. Statins, commonly used as lipid-lowering agents, have emerged as attractive repurposed drug candidates due to their ability to interfere with fungal ergosterol biosynthesis and Ras-mediated signaling pathways. However, repurposed statins face major translational barriers, including poor water solubility, limited mucosal bioavailability, and dose-dependent systemic toxicity. Nanotechnology-driven delivery platforms offer versatile solutions to these challenges, enabling site-directed delivery, improved stability, enhanced permeability, and controlled release. Lipid and polymeric nanocarriers, particularly chitosan-based nanoparticles, enable controlled release and prolonged mucosal retention, making them suitable for localized antifungal therapy. This review explores the integration of statin repurposing with advanced drug delivery strategies as a novel therapeutic paradigm for mucosal candidiasis. Updated evidence demonstrating the antifungal potential of nano-formulated statins is summarized, in conjunction with a general overview of design aspects relevant to optimizing delivery systems. Although still in early stages of investigation, this synergistic approach holds promise for overcoming resistance mechanisms and reducing the recurrence rates associated with existing antifungals. Ultimately, leveraging drug repurposing alongside nanotechnology may accelerate the translation of statin-based antifungal therapies into clinical practice, providing an innovative and cost-effective avenue to broaden the therapeutic arsenal against mucosal Candida infections.

Anxiety disorders rank among the most prevalent mental health conditions worldwide, significantly affecting patients' lives. They are frequently comorbid with other psychiatric disorders, often exacerbating their severity. Current pharmacological treatments; selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines, remain limited in efficacy and are associated with undesirable side effects, underscoring the urgent need for alternative therapeutic approaches. However, progress in developing new treatments has been hindered by an incomplete understanding of the neural mechanisms underlying these disorders. Bridging this knowledge gap requires advanced research tools capable of providing deeper insight into the neural circuits involved in anxiety. Fiber photometry (FP) has emerged as a powerful and cost-effective technique for measuring neural activity in freely moving animal models. By enabling real-time monitoring of calcium dynamics in specific neural populations within defined brain regions, this method offers invaluable insights into both normal physiological processes and pathological states. In this review, we first present an accessible introduction to FP, detailing its apparatus, procedures, and key advantages and limitations. We then conducted a comprehensive analysis of 39 studies indexed in PubMed that have employed FP to investigate neural circuits implicated in anxiety. Our review reveals the techniques' significant contributions across different research domains, including physiological (33%), pathological (53%), and dual-purpose studies (13%). Beyond summarizing its utility, our goal is to make FP more accessible to researchers. By providing a foundational guide for its integration into future scientific projects, we aim to facilitate advances in anxiety research and contribute to the development of novel therapeutic strategies.

Ait Tayeb, AEK, Laforgue, E-J, Schreck, B, et al., ABCB1, SLC22A1, COMT, and OPRM1 genotypes: Study of Their Influence on Plasma Methadone Levels and Clinical Response to Methadone Maintenance Treatment in Opioid Use Disorder. Fundamental & Clinical Pharmacology 2025; 39(3):e70013, https://doi.org/10.1111/fcp.70013.

Two authors (Caroline Victorri-Vigneau and Céline Verstuyft) have been deleted from the authors list in the original published version of this article.

Caroline Victorri-Vigneau and Céline Verstuyft's names have been corrected and added to the author's list of the original published version.

We apologize for this error.

Chronic kidney disease (CKD) affects over 10% of the world's population and is associated with high morbidity and mortality rates. The management of CKD is complex; CKD alters drug pharmacokinetics and pharmacodynamics and further complicates therapeutic strategies regimens. Uremic toxins accumulate in patients with CKD and significantly impact drug pharmacokinetics and drug responses. These toxins modify drug pharmacokinetics. Indeed, uremic toxins can alter intestinal absorption by affecting drug transporters, such as P-glycoprotein and multidrug resistance–associated proteins. These changes modify the bioavailability of drugs and change drug absorption profiles in patients with CKD. Furthermore, uremic toxins interfere with drug distribution and metabolism. For instance, the urea-driven carbamylation of albumin can reduce drug-binding sites on this plasma protein and thus increase the free drug fraction. In the liver, CKD can reduce the expression of cytochrome P450 enzymes and thus impair drug biotransformation. Furthermore, uremic toxins can interact with cellular transporters, affecting drug clearance and leading to drug accumulation. In terms of pharmacodynamics, uremic toxins can alter receptor function and impair drug effectiveness. The blood–brain barrier may also be disrupted by the accumulation of toxins; this enhances drug penetration into the brain and increases the risk of adverse effects. After providing a brief summary of the various drug elimination pathways and the definitions and classification of uremic toxins, we shall use examples to illustrate the potential impact of a decrease in glomerular filtration rate (GFR) and/or an increase in uremic toxin levels on drug pharmacokinetics and pharmacodynamics.

In the 1950s–60s, serotonergic psychedelic drugs were studied as potential adjuvants to psychotherapy to treat addiction and alcoholism. However, starting in the 70s, preclinical and clinical studies on psychedelics stopped for decades because legislation controlled its recreational use, citing their hallucinogenic and psychotomimetic effects, as well as their abuse potential. Amazingly, we are witnessing an impressive return of these drugs due to recent clinical trials suggesting a therapeutic potential of psychedelics, among them psilocybin, for treating patients with depression resistant to conventional antidepressant drugs. Yet, their underlying mechanisms of action remain incompletely elucidated. This review provides an update on seminal clinical trials using psilocybin, as well as preclinical work uncovering the pharmacological properties and experimental pharmacology of psilocybin and its active metabolite psilocin. These drugs are primarily serotonin 5-HT_2A receptor (5-HT2AR) agonists. Although there is a consensus that 5-HT2AR activation mediates its psychedelic effects in human and rodent models of anxiety/depression, its role in psilocin's antidepressant effects remains controversial. This review also provides an overview of neurotransmitter systems, neuroplasticity, and neural circuits activated by psilocin. Further research in developing effective antidepressants for depression is prescient now more than ever, as according to the World Health Organization (WHO), depression will be the main cause of disability in 2030. Understanding the mechanisms through which psilocybin/psilocin would be an effective antidepressant is crucial to ultimately validate its therapeutic potential when combined with SSRIs/SNRIs in mood disorders.