Fundamental & Clinical Pharmacology最新文献

Pharmacotherapy for major anxiety disorders continues to present dangerous side effects, complicating precise treatment choices for each patient. In this context, β-caryophyllene (BCP), a selective agonist of the cannabinoid type II receptor (CB2R), is recognized as a safe immunomodulatory drug. CB2R has recently been identified in glutamatergic and dopaminergic neurons, supporting its potential as a pharmacotherapy for mood disorders. Thus, we propose to investigate the effects of systemic BCP treatment (50, 100, and 200 mg/kg) on anxiety-like behavior. To this end, we utilized 92 adult male Swiss mice across two acute and one chronic pharmacological assay using the 3D maze test. In the acute assay, 30 min after treatment (BCP or vehicle), we conducted the One-Trial Protocol (OTP) lasting 12 min and the Two-Trial Protocol (TTP) lasting 12 min (comprising two trials of 5 min, with a 2-min interval between them). In the chronic assay, after 10 days of treatment (once daily; BCP or vehicle), testing was performed over five consecutive days (once daily; 12 min), 30 min after administration of BCP or vehicle. Additionally, locomotion was assessed. Under these conditions, we observed no effects on locomotion, anxiety-like behavior, or anxiety-like extinction behavior following either acute or chronic oral administration of BCP. Furthermore, we propose the use of TTP in the 3D maze as a valuable method for assessing acute pharmacological effects in mice. Lastly, behavioral modulation induced by CB2R agonists, particularly BCP, must be further investigated to better understand its potential neurological treatment applications and associated side effects.

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.