Future Pharmacology

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental condition, and pharmacogenetic studies aim to clarify interindividual variability in treatment responses and adverse effects. Despite increasing research, the field remains fragmented. This review provides a bibliometric analysis of ADHD pharmacogenetics (2005–2025), identifying its intellectual foundations, thematic structure, and global distribution. Methods: A bibliometric search was conducted in Scopus and Web of Science, retrieving 711 documents published between 2005 and July 2025. Data were analyzed with the Bibliometrix R package and Biblioshiny interface, applying bibliometric mapping, Bradford’s Law, co-word analysis, and thematic mapping. Only peer-reviewed journal articles, books, and book chapters were included to ensure scientific rigor. Results: The dataset shows a modest annual growth rate but strong impact, with an average of 29.6 citations per article. Highly cited works converge into four domains: (i) clinical guidelines and pharmacological treatments; (ii) cognitive heterogeneity and subtypes; (iii) neurodevelopmental and genetic mechanisms; (iv) environmental and health-related influences. Geographically, the United States leads with 24.8% of publications, followed by Brazil, China, and European countries. Keyword analysis reveals two main clusters: a clinical–therapeutic pole (methylphenidate, atomoxetine, child) and a genetic–molecular pole (dopamine transporter, SNPs, genotype). Conclusions: ADHD pharmacogenetics shows consolidation with strong clinical and genetic cores but limited integration of comorbidity, adult populations, and non-stimulant treatments. Future research should prioritize multi-center cohorts, multi-omic designs, and stronger international collaboration to advance precision medicine in ADHD. Full article

Background: Staphylococcus aureus is a clinically relevant pathogen with a strong ability to form biofilms on a wide range of surfaces, which markedly reduces the effectiveness of antimicrobial treatments and contributes to therapeutic failure. Although essential oils (EOs) represent effective and economical antimicrobial alternatives, their clinical application is limited by rapid oxidation, volatility, and potential cytotoxicity. In this context, nanoencapsulation emerges as a promising strategy to improve EO stability, control release, and reduce toxicity. In this study, Tetradenia riparia essential oil was encapsulated into poly(lactide) (PLA) nanoparticles (NP) using the nanoprecipitation method. Methods: The physicochemical properties of the nanoparticles were characterized, and their antibacterial, antibiofilm, and cytotoxic activities were evaluated. Antibiofilm and antibacterial effects against S. aureus were assessed by the broth microdilution method, while cytotoxicity was determined using a VERO cell line. Results: The nanoparticles exhibited nanometric size, spherical morphology, and homogeneous structure. Both free EO and EO-loaded nanoparticles demonstrated antibacterial and antibiofilm activity against S. aureus. Importantly, EO-loaded nanoparticles were significantly less cytotoxic than free EO. Nanoencapsulation effectively prevented rapid EO evaporation and degradation, thereby enhancing stability. The nanoparticles exhibited a zeta potential of approximately −23.1 mV, indicating adequate colloidal stability. Differential scanning calorimetry revealed a reduction in melting enthalpy from 429.63 J/g (blank nanoparticles) to 115.83 J/g for EO-loaded nanoparticles, indicating decreased polymer crystallinity and a system favorable for controlled EO release. Conclusions: Overall, these findings demonstrate that nanoencapsulation of T. riparia essential oil into PLA nanoparticles preserves antimicrobial efficacy, reduces cytotoxicity, and improves physicochemical stability, supporting the potential of this nanostructured system as a promising strategy for the treatment of S. aureus biofilm-associated infections. Full article

Background: Neuroblastoma is the most common extracranial solid malignancy in infants and children. High-risk neuroblastoma patients are commonly treated with temozolomide (TMZ), which typically exhibits a poor therapeutic response. Serotonin, also known as 5-hydroxytryptamine (5-HT), plays various essential functions in the human body. In the central nervous system, it serves as a neurotransmitter. Beyond its physiological roles, 5-HT has recently been identified as a potential growth factor for several human tumors, including gliomas and carcinoid tumors. Recent literature has demonstrated that 5-HT receptor antagonists can inhibit the growth of cancer cells. Furthermore, both 5-HT receptors and their antagonists have been identified as potential anticancer agents, suggesting their significance in the development of new treatment strategies. Objectives: The primary aim of this study was to examine the effects of 5-HT and 5-HT antagonists on tumor (neuroblastoma (SH-SY5Y)) and healthy cells (microglia (HMC3)) and determine the impact of their interaction with the anticancer agent TMZ on cell proliferation/viability and migration. Methods: The study explored the interaction between 5-HT, the 5-HT antagonist granisetron (GRN), the anticancer agent TMZ, and their combinations, specifically assessing their influence on cell proliferation, viability, and migration. Results: As a result, the single and combined applications of 5-HT, TMZ, and GRN, a 5-HT antagonist, inhibited cell growth and proliferation in SH-SY5Y, causing decreased cell viability. Additionally, the combination of 5-HT and GRN increased the efficacy of TMZ. Conclusions: The study findings revealed that 5-HT and 5-HT antagonists may have therapeutic effects by exhibiting antiproliferative effects in SH-SY5Y cells at high concentrations. Full article

The treatment of diabetes in the modern era, with its growing patient population, represents a significant challenge due to the wide range of adverse effects associated with medications that target complex biochemical processes. Consequently, researchers are investigating the hypoglycemic potential of existing drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, fever, and various inflammatory conditions. Recent studies have shown that NSAIDs, particularly salicylates, can influence glycemia through multiple mechanisms, including inhibition of gastrointestinal enzymes, blockade of K_ATP channels, activation of AMP-activated protein kinase (AMPK), and inhibition of NF-κB signaling, among others. Accordingly, this review explores the hypoglycemic potential of NSAIDs as well as their derivatives, and the diverse mechanisms through which these molecules may influence glucose homeostasis. Full article

Background/Objectives: Leishmaniasis is a neglected parasitic disease with significant global impact and limited therapeutic options due to the toxicity and cost of current treatments. Antimicrobial peptides (AMPs) derived from amphibians, such as Ocellatin-PT4 and Ocellatin-PT6, have emerged as promising bioactive molecules due to their antimicrobial properties and low toxicity to mammalian cells. This study evaluated the leishmanicidal and immunomodulatory effects of Ocellatin-PT4 and Ocellatin-PT6 against Leishmania amazonensis amastigotes. Methods: Peptides were tested on axenic amastigotes and macrophages infected with amastigotes. Cytotoxicity was assessed using MTT (0.4–197 µM for Ocellatin-PT4 and 0.3–152.1 µM for Ocellatin-PT6) and vital dye exclusion assays. Reactive oxygen species (ROS), nitric oxide (NO), and lipid droplet (LD) production were quantified to assess immunomodulatory responses. Results: Ocellatin-PT4 and Ocellatin-PT6 significantly reduced the viability of free and intracellular amastigotes at concentrations ≥ 24.7 µM and ≥19 µM, respectively, without affecting J774 macrophage viability. Infected macrophages treated with the peptides showed reduced parasite load and decreased infection index (≥12.3 µM for Ocellatin-PT4 and ≥2.4 µM for Ocellatin-PT6). Both peptides modulated the oxidative stress response: they reduced ROS levels in infected macrophages while only slightly increasing NO production at higher concentrations. Additionally, lipid droplet accumulation, which was increased during infection, was downregulated by both peptides—particularly by Ocellatin-PT6. Conclusions: Ocellatin-PT4 and Ocellatin-PT6 exert leishmanicidal effects and modulate key macrophage functions without cytotoxicity. These peptides represent promising candidates for the development of novel therapies against cutaneous leishmaniasis. Full article

The progress of contemporary pharmacology is deeply linked to pharmacokinetics (PK) and its quantitative exploration through PK modeling. By offering a robust mathematical framework to describe and predict drug absorption, distribution, metabolism, and excretion (ADME), PK modeling is essential for designing and optimizing safe and effective dosing regimens and for advancing personalized medicine and model-informed drug development (MIDD). The reliability of population PK (popPK) and physiologically based PK (PBPK) models depends on high-quality experimental data to estimate PK parameters. Traditional PK data sources include clinical studies, preclinical animal models, and human-derived cell lines. Although considered gold standards, these sources have significant drawbacks. Clinical trials are often restricted by ethical, logistical, and financial challenges and often include homogenous populations that fail to reflect real-world interindividual variability. Similarly, animal and cell-based models lack the physiological complexity of humans, leading to discrepancies between preclinical predictions and clinical outcomes. These constraints have stimulated interest in alternative platforms that more faithfully recapitulate human physiology and interindividual diversity. This review explores the potential of organoids as a novel or complementary source of PK-relevant data. Organoids, three-dimensional (3D) stem cell-derived structures, mimic the cellular architecture, functional heterogeneity, and physiological responses of human tissues. In particular, intestinal, liver, and kidney organoids preserve essential cellular features of ADME processes, positioning them as promising tools for integration into popPK and PBPK modeling frameworks. Full article

Background/Objectives: Fungal keratitis (FK) is a current challenge in ophthalmology due to its association with severe visual impairment and the limitations of current antifungal therapies. We aim to evaluate the antifungal activity of essential oils (EOs) from the aromatic and medicinal plants Cymbopogon citratus and Lavandula pedunculata against selected FK pathogens collected from FK patients in two Portuguese hospitals. Methods: The antifungal activity of the EOs was tested at concentrations of 25%, 50%, 75%, and 100% for up to 7 days using the solid-phase disk diffusion in vitro assay. Results: Candida albicans was the most prevalent pathogen (28.6%), followed by Candida parapsilosis (21.4%) and Dicyma olivacea (14.2%). The other identified species were Aspergillus fumigatus and Scedosporium boydii (7.1%). Clinical diagnostic methodologies showed agreement with the molecular identification. Cymbopogon citratus EO showed higher antifungal activity than Lavandula pedunculata EO. The highest antifungal activity was observed against Aspergillus fumigatus and Scedosporium boydii (inhibition zone diameter, IZD = 90.0 mm) after 7 (Cymbopogon citratus EO) or 3 days of incubation (Lavandula pedunculata EO). While the antifungal activity of Cymbopogon citratus EO was maintained during the study (for Aspergillus fumigatus, Candida albicans, and Scedosporium boydii), the antifungal activity of Lavandula pedunculata EO decreased with time. Conclusions: Cymbopogon citratus EO and Lavandula pedunculata EO showed optimal antifungal activity against molds (Aspergillus fumigatus and Scedosporium boydii) after 3 days of incubation. Against yeasts (Candida albicans and Candida parapsilosis), the EOs showed lower activity. Our study sheds light on the development of new pharmacological strategies for FK based on EOs extracted from aromatic and medicinal plants. Full article

Background: Rapidly growing mycobacteria (RGM) are microorganisms with variable pathogenicity, which can cause different clinical forms of mycobacterioses. They can form structured communities at the liquid-air interface and adhere to animate and inanimate solid surfaces, characterizing one of their most powerful mechanisms of resistance and survival, named biofilms. Objectives: Here, a novel series of sulfamethoxazole (SMTZ) Schiff bases were obtained by the condensation of the primary amine from SMTZ core with six different aldehydes to evaluate their antimicrobial and antibiofilm activities, as well as physicochemical and in silico characteristics. Methods: The compounds L1–L6 included: pyridoxal hydrochloride (L1), salicylaldehyde (L2), 3-methoxysalicylaldehyde (L3), 2-hydroxy-1-naphthaldehyde (L4), 3-allylsalicylaldehyde (L5), and 4-(diethylamino)salicylaldehyde (L6). MIC determination was performed against standard strains and seven clinical isolates. Time-kill assays, biofilm inhibition assays, atomic force microscopy, and peripheral blood mononuclear cell cytotoxicity assays were carried out. Density functional theory (DFT) calculations using quantum descriptors, Mulliken charges, Fukui functions, non-covalent interactions (NCI), and reduced density gradient (RDG), along with molecular docking calculations to DHS, LasR, and PqsR, supported the experimental trend. Results: The compounds L1–L6 showed a significant capacity to inhibit the growth of RGM, with MIC values in the range of 0.61 to 1.22 μg mL⁻¹, which are significantly lower than those observed for the parent compound SMTZ, demonstrating superior antimicrobial potency. To deepen antimicrobial activity assays, L1 was chosen for further evaluations and showed a significant ability to inhibit the growth of RGM in both planktonic and biofilm forms. In addition, atomic force microscopy views great changes in topography, electrical force, and nanomechanical properties of microorganisms. The cytotoxic assays with the peripheral blood mononuclear cell model suggest that the new compound may be considered as an antimicrobial alternative, as well as a safe substance showing selectivity indexes in the range of efficacy. Conclusions: Density functional theory (DFT) calculations were performed to obtain quantum descriptors, Mulliken charges, Fukui functions, non-covalent interactions (NCI), and reduced density gradient (RDG), which, with molecular docking calculations to DHS, LasR, and PqsR, supported the experimental trend. Full article

Introduction: Bacterial infections, especially those caused by multidrug-resistant strains, remain a major health concern. This study investigates 4-chlorobenzyl p-coumarate, assessing its antibacterial mechanism, pharmacokinetic profile, and potential to modulate antimicrobial resistance. Methods: In silico studies were conducted, including molecular docking, molecular dynamics simulations, and pharmacokinetic predictions, alongside in vitro assays assessing efflux pump inhibition, antibiotic modulation, and bacterial DNA analysis. Results: The compound showed higher binding affinity and complex stability with the enzyme phosphatidylglycerol phosphate synthase, while also exhibiting reduced residue fluctuations and better flexibility with the NAD⁺-dependent DNA ligase. Molecular interactions with the efflux proteins MepA and NorA were also observed. Pharmacokinetic predictions indicated a favorable profile, including suitability for oral administration. Experimentally, the compound inhibited the MepA and NorA efflux pumps, modulated the activity of the antibiotics ciprofloxacin and norfloxacin, and reduced DNA concentration in treated cells. Conclusions: The findings suggest that the compound acts through dual mechanisms, with a prediction of activity by disrupting phosphatidylglycerol synthesis and DNA replication while inhibiting and modulating MepA and NorA efflux pumps. Full article

Levosimendan, a calcium-sensitizing inodilator, has emerged as a promising adjunctive therapy in patients undergoing veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Its pharmacodynamic profile, combining positive inotropy with vasodilation and mitochondrial protective effects, offers a unique therapeutic potential in the context of mechanical circulatory support. Despite growing interest, the clinical impact of Levosimendan in ECMO remains debated, with heterogeneous evidence regarding its efficacy in improving weaning success, reducing vasopressor requirements or mitigating ischemia-reperfusion injury. This narrative review aims to critically appraise the current literature on Levosimendan use in ECMO settings, exploring its mechanistic rationale, pharmacologic behavior under extracorporeal circulation and potential role in various clinical scenarios including post-cardiotomy shock and refractory cardiogenic failure. The limitations of existing studies are critically examined, underscoring the need for high-quality clinical trials to define appropriate patient selection, optimal timing of administration and dosing strategies. This review synthesizes current evidence to determine whether Levosimendan constitutes a true therapeutic asset or remains merely an adjunctive agent in the complex management of ECMO supported patients. Full article

The global spread of Monkeypox virus (MPXV) has emerged as a major public health concern, with the 2022 outbreak underscoring the urgent need for effective antiviral therapies. Current treatment options are limited because no drugs specifically target Mpox, and existing recommendations rely on repurposed smallpox antivirals that may cause resistance. This highlights the critical need for novel therapeutic agents targeting key viral and host factors involved in MPXV pathogenesis. Medicinal plants provide a rich reservoir of bioactive compounds with potential antiviral activity, particularly in low- and middle-income countries where they play an essential role in healthcare. To address this issue, we conducted a review exploring innovative in silico approaches for natural product-based drug discovery against MPXV. Computational studies identified phytochemicals such as curcumin, punicalagin, rosmarinic acid, and quercitrin with strong affinities for key viral proteins including DNA polymerase, TMPK, DdRp, A42R, MTase, p37, and envelope proteins and favorable pharmacokinetic profiles Despite these promising findings, fragmented biological datasets, viral mutability, and limited in vitro and in vivo validation hinder clinical translation. Our analysis highlights integrating AI-driven virtual screening with experimental validation to accelerate MPXV drug discovery, providing a scalable framework for managing emerging viral threats. Full article

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and cognitive impairments due to dopaminergic neuron loss. The neurotoxin MPTP is commonly used to model PD, as it selectively targets these neurons. Quercetin (QU), a flavonoid with antioxidant properties, has shown neuroprotective potential, but its poor solubility limits clinical application. Nanoemulsions (NEQU) have emerged as a strategy to enhance its bioavailability and efficacy. Methods: To evaluate the neuroprotective and antioxidant effects of QU and NEQU, zebrafish larvae were exposed to MPTP (50 µM) and assessed for survival, locomotion (total distance traveled), morphological parameters, reactive oxygen species (ROS), lipid peroxidation (via MDA), and reduced glutathione (GSH) levels. Results: Only NEQU pre-treatment reversed MPTP-induced locomotor deficits. Both QU and NEQU (2.5 µM) significantly reduced ROS production and lipid peroxidation, with no effect on GSH levels. Notably, MPTP exposure led to a significant reduction in head size, an unprecedented finding in zebrafish PD models, indicating neurotoxicity. Morphometric analysis showed no change in total body length. However, MPTP significantly decreased swim bladder size and increased yolk sac size. Treatment with QU and NEQU attenuated these swim bladder alterations; no significant differences were observed in other parameters. Conclusions: These findings suggest that quercetin, particularly when nanoencapsulated, is a promising candidate for further development as a therapeutic agent to mitigate PD-related neurodegeneration. Full article

Background: Tetrabenazine, a VMAT2 inhibitor used for hyperkinetic disorders, shows considerable pharmacokinetic variability due to extensive first-pass metabolism. Standardization of clinical trial conditions, including posture, may reduce variability and improve bioequivalence assessments. Objective: The aim of this study was to determine the impact of postural restriction on the pharmacokinetics of tetrabenazine and its active metabolite, dihydrotetrabenazine (HTBZ), under controlled conditions. Methods: A randomized, open-label, four-period replicate crossover study enrolled 72 healthy fasted adults who received a single 25 mg tetrabenazine dose under two conditions: 4 h semirecumbent posture versus unrestricted movement. Plasma drug concentrations were measured across 36 h using validated LC–MS/MS method. Pharmacokinetic parameters were estimated via non-compartmental analysis and compared with Wilcoxon signed-rank tests. Results: Postural restriction significantly increased tetrabenazine exposure (AUC_0–t: +16.4%, p < 0.0001) and half-life (p = 0.002), with a nonsignificant rise in C_max. For HTBZ, C_max decreased (−16.2%, p = 0.018), whereas AUC was unchanged. Parent-to-metabolite ratios increased by 24–29%. Replicate design analyses showed reduced intra-subject variability for tetrabenazine AUC with posture control (~24% vs. >28%). Simulation suggested that posture restriction could lower sample size requirements by 15–30% in two-period average bioequivalence trials. Conclusions: Maintaining a semirecumbent posture after dosing enhances tetrabenazine’s bioavailability, attenuates early metabolite formation, and reduces pharmacokinetic variability. Incorporating posture control into bioequivalence trial protocols may optimize study design, reduce participant exposure, and align with ICH-GCP ethical principles. Full article

Background/Objectives: Janus kinase 2 (JAK2) is a pivotal signaling protein implicated in various hematological malignancies and inflammatory disorders, making it a compelling target for therapeutic intervention. Methods: In this study, we employed an integrative computational approach combining ligand-based screening, pharmacophore modeling, molecular docking, molecular dynamics (MD) simulations, and MM/PBSA free energy calculations to identify JAK2 inhibitors from the ChEMBL database. A comprehensive virtual screening of over 1,900,000 compounds was conducted using Tanimoto similarity and a validated pharmacophore model, resulting in the identification of 39 structurally promising candidates. Docking analyses prioritized compounds with favorable interaction energies, while MD simulations over 100 ns assessed the dynamic behavior and binding stability of top hits. Results: Four compounds, CHEMBL4169802, CHEMBL4162254, CHEMBL4286867, and CHEMBL2208033, exhibited consistently superior performance, forming stable hydrogen bonds, favorable RMSD profiles (≤0.5 nm), and strong binding interactions, including salt bridges. Notably, the binding free energies revealed ΔG values as low as −29.91 kcal/mol, surpassing that of the reference inhibitor, momelotinib (−24.17 kcal/mol). Conclusions: Among these, CHEMBL4169802 emerged as the most promising candidate due to its synergistic electrostatic and hydrophobic interactions. Collectively, our results highlight these compounds as probable, JAK2-selective inhibitors with strong potential for further biological validation and optimization. Full article

Background/Objectives: Neuroblastoma is a pediatric embryonal tumor of the autonomic nervous system, characterized by high heterogeneity. Recent research has explored the therapeutic potential of retinoic acid and selenium derivatives as antiproliferative agents. This study aims to assess the antiproliferative effects of sodium selenite and retinoic acid, as well as the conventional chemotherapeutic agents, cyclophosphamide and cisplatin, using the SH-SY5Y neuroblastoma cell line. Methods: Cells were treated with the compounds at concentrations ranging from 0 to 1000 µM for 72 h. The following assays were performed: cell viability, clonogenic assay, cell migration, cell cycle analysis, and gene expression (BCL2 and BAX). Data were analyzed using the Kruskal–Wallis test followed by Dunn’s or the Mann–Whitney test (p < 0.05). IC₅₀ values were obtained from dose–response curves. Results: Sodium selenite (100–1000 µM) significantly reduced cell viability by more than 50% (IC₅₀: 166 µM at 72 h). Retinoic acid (300 µM) reduced viability by 65% (IC₅₀: 198 µM at 72 h), and cisplatin (10 µM) reduced viability by 79% (IC₅₀: 3.4 µM at 72 h). All compounds significantly decreased colony formation. Sodium selenite and retinoic acid induced arrest in the G0/G1 phase of the cell cycle. Gene expression analysis revealed downregulation of the BCL2 gene by all compounds and upregulation of BAX only by sodium selenite at IC₅₀ concentration. Conclusions: Sodium selenite and retinoic acid showed antiproliferative effects on neuroblastoma cells, suggesting their potential as adjuvant therapeutic agents. To reach this goal, we suggest further investigation of their mechanisms of action and evaluation of the combined strategies. Full article

Background/Objectives: Fouquieria splendens Engelm. is a medicinal plant traditionally used in North America for treating metabolic disorders; however, its antihyperglycemic properties and safety profiles remain poorly studied. We investigated the phytochemical composition, oral acute toxicity, mutagenicity, and antihyperglycemic activity of the foliar ethanolic extract of F. splendens (EFS). Methods: Phytochemical analysis was performed using ultra-performance liquid chromatography–mass spectrometry. Acute toxicity and mutagenicity were evaluated following the OECD guidelines. Antihyperglycemic activity was assessed in streptozotocin-induced diabetic rats treated with EFS (200 mg/kg) alone or in combination with metformin for 30 days. Results: Eleven phenolic compounds were identified in the EFS, including ellagic acid, morin, apigenin, and luteolin 7-Oglucoside. EFS was non-mutagenic and had an LD₅₀ of >2000 mg/kg. This treatment significantly reduced blood glucose levels and enhanced the effect of metformin in diabetic rats. Histopathological analysis showed preserved morphology in the pancreatic, hepatic, and renal tissues of the treated animals. Conclusions: EFS exhibited significant antihyperglycemic activity and a favorable safety profile, supporting its potential as a complementary phytotherapeutic agent for diabetes management. These results highlight the pharmacological value of F. splendens and promote the exploration of native plants as adjuncts for chronic disease therapy. Full article

Peripheral nerve injuries can lead to significant functional impairments, and treatment options remain limited. Galantamine, widely used for cognitive disorders, has shown potential effects on the peripheral nervous system, making it a candidate for new therapeutic approaches. The narrative review explores the use of galantamine for peripheral nerve injuries, with a focus on transdermal and iontophoretic delivery methods. Searches in scientific databases revealed no peer-reviewed publications addressing this specific application. As a result, the review expanded to include printed and offline sources and a broader timeframe to capture earlier reports. Available evidence from Bulgaria suggests that galantamine ampules have been applied via iontophoresis for peripheral neuropathy. However, this approach is not documented in established scientific databases, and information on its safety and effectiveness is limited. Overall, research on transdermal galantamine for peripheral nerve injuries is still scarce. More studies are needed to better understand its potential benefits and to optimize safe delivery methods. Full article

Background/Objectives: The antiseizure effects of cannabidiol (CBD) were extensively studied when used as a monotherapy. However, there is conflicting evidence regarding its use in combination with levetiracetam (LEV). Methods: This study explored the effects of chronic co-administration of CBD and LEV in a pentylenetetrazole-kindling rat model to evaluate potential antiseizure and neuropsychiatric interactions. Male and female Wistar rats (n = 48) were divided into four treatment groups: one control and three treated by receiving LEV 300 mg/kg and LEV + CBD at 10 and 60 mg/kg, respectively. Seizure parameters were assessed using the Racine scale, and behavior was evaluated using the open field (OF), novel object recognition (NOR), and social interaction (SI) tests. Results: While both combinations, LEV + CBD 10 mg/kg and 60 mg/kg, significantly reduced maximal seizure intensity, the LEV + CBD 10 mg/kg attenuated LEV’s anti-kindling effect. Additionally, only LEV + CBD 60 mg/kg reduced seizure duration compared to LEV alone (p = 0.0002). In behavioral assessments, LEV + CBD 10 mg/kg showed anxiolytic effects in the OF test by increasing central activity (p = 0.0141). In contrast, the LEV + CBD 60 mg/kg impaired social behavior in both sexes (p = 0.0019). LEV improved the cognitive performance of female rats in the NOR test (p = 0.0301), but this improvement was not observed in LEV + CBD groups. Conclusions: CBD exhibited dose-dependent effects when combined with LEV: low doses might offer anxiolytic effects but promote kindling, and high doses enhance seizure control but potentially worsen social interaction. The results support the therapeutic potential of LEV-CBD co-treatment, while highlighting the need for careful dose optimization when considering CBD as an adjunctive therapy. Full article

Introduction: Linezolid is a reserve antibiotic used to treat infections caused by Gram-positive bacteria with resistance genes. In critically ill patients, high intra- and interindividual variability has been observed, prompting the search for alternative methods to reduce this variability and achieve the pharmacokinetic/pharmacodynamic indices necessary for a favorable efficacy–safety balance. Aim of the study: We wished to compare the safety and effectiveness of a continuous infusion (CI) versus an intermittent infusion (II) of linezolid in patients requiring intensive care. Materials and Methods: This study, registered under the number NCT05801484), was a prospective, open-label, single-center, two-arm study. Data on hematologic safety and effectiveness were collected and compared between patients receiving CI and II, respectively, at the same daily dose of linezolid (1200 mg). Results: Twenty-nine patients from the intensive care unit were included, divided into two groups. No statistically significant difference was found in 30-day mortality between the groups, nor in the likelihood of post-treatment culture negativity. However, a significantly greater reduction in C-reactive protein levels was observed in the CI group compared to the II group. Regarding safety, at CrCl < 60 mL/min, the decrease in platelets was statistically significant in group II but not in group CI. Additionally, at the 30-day follow-up, recovery from thrombocytopenia was better in the CI group. Conclusions: Continuous infusion of linezolid proved to be non-inferior to intermittent infusion at the same daily dose in terms of effectiveness. Furthermore, a lower risk of adverse reactions was identified with continuous infusion. Full article