Antiarrhythmic drug therapy in cardiomyopathies remains challenging because arrhythmic risk, drug efficacy, and pro-arrhythmic vulnerability vary substantially across phenotypes. This review summarizes contemporary guideline and consensus recommendations on antiarrhythmic drug use in hypertrophic, dilated, non-dilated left ventricular, and arrhythmogenic cardiomyopathies.

Epileptogenesis is increasingly recognized as a multifactorial process driven by persistent neuroinflammation, oxidative stress, and dysregulated intracellular signaling, highlighting the need for therapeutic strategies that extend beyond symptomatic seizure control. The present study investigated the potential effects of prophylactic carvedilol administration on behavioral seizure progression and associated pathological alterations during the PTZ-induced kindling model, with particular emphasis on inflammatory and signaling pathways implicated in epileptogenesis. Repeated PTZ administration resulted in progressive behavioral seizure development, impaired open-field performance, hippocampal neuronal damage, reduced GABA levels, increased oxidative stress and inflammatory mediators, and altered hippocampal NLRP3 expression, along with changes in PI3K-, AKT-, and mTOR-related protein expression. Carvedilol treatment was associated with lower behavioral seizure scores, improved open-field performance, preservation of hippocampal architecture, restoration of GABA content, and attenuation of oxidative and inflammatory alterations. Carvedilol treatment was also accompanied by reduced NLRP3 levels and changes in PI3K/AKT/mTOR-related measurements. These findings demonstrate associations between carvedilol treatment and multiple pathological processes during PTZ-induced kindling, but do not establish direct pathway-specific causality.

Despite the potential of current cancer immunotherapies, tumor cells frequently evade immune surveillance by forming an immunosuppressive microenvironment, leading to treatment resistance. Current inquiry positions the sympathetic nervous system (SNS) at the forefront of tumor immunology as a critical driver of this immune evasion. This review delineates the cellular pharmacology of SNS-mediated immune regulation across the tumor ecosystem. Operating predominantly through the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling axis, the SNS engages in bidirectional regulation with immune cells of the tumor microenvironment (TME). Norepinephrine and epinephrine interact with β2-adrenergic receptors (β2-ARs), triggering G-protein dissociation, adenylyl cyclase stimulation, and cAMP generation. This pharmacological cascade promotes the polarization of macrophages to the M2 phenotype, hinders dendritic cell maturation, impairs natural killer (NK) cell function, fosters the differentiation of regulatory T cells (Tregs), and suppresses the effector activity of CD8[+] T cells. Consequently, we evaluate the translational prospects of repurposing β-blockers as potent anti-cancer immunomodulators. Preclinical evidence demonstrates that pharmacological blockade of β2-AR signaling can reverse these immunosuppressive effects, augmenting intratumoral CD8[+] T-cell infiltration and enhancing the efficacy of immune checkpoint inhibitors (ICIs). Ultimately, engineering multimodal combination regimens-guided by multi-omics biomarker stratification-offers a novel trajectory to overcome resistance, restore therapeutic sensitivity, and advance precision cancer immunotherapy.

There is no effective treatment for cognitive impairment after traumatic brain injury (TBI). Previous studies have demonstrated that propranolol may improve cognitive function. The glymphatic system plays a crucial role in cognitive impairment after TBI. Thus, we explored the mechanism by which propranolol improves cognitive function and promotes glymphatic system recovery after TBI. In vivo, rats were subjected to controlled cortical impact (CCI) and treated with saline, propranolol, S31-201 (an inhibitor of STAT3) and SB-3CT (an inhibitor of MMP2) respectively. Rats then underwent a battery of cognitive tests. We also assessed white matter (WM) integrity and glymphatic system function. The expression of phosphorylated tau (p-tau), amyloid-β (Aβ), aquaporin 4 (AQP4), signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p-STAT3), and matrix metalloproteinase-2 (MMP2) was evaluated by immunocytochemistry and Western blot. In vitro, the levels of STAT3, p-STAT3, MMP2 and AQP4 were assessed after astrocytes were treated with propranolol, noradrenaline, S31-201 and SB-3CT respectively. In vivo results showed that propranolol, S31-201 and SB-3CT improved cognitive function and restored glymphatic system function after TBI. The deposition of p-tau and Aβ was decreased, and WM integrity was restored in TBI rats treated with propranolol, S31-201 and SB-3CT. Propranolol, S31-201 and SB-3CT induced the overexpression of AQP4 in blood vessels and astrocytes after TBI. In addition, the levels of p-STAT3 and MMP2 were knocked down in propranolol-treated TBI rats. In vitro, propranolol reversed the upregulated expression of p-STAT3 and MMP2 in noradrenaline-treated astrocytes. The noradrenaline-induced impairment of AQP4 expression in astrocytes was antagonized by propranolol, S31-201 and SB-3CT. In conclusion, propranolol may improve cognitive function and facilitate glymphatic system functional recovery after TBI through the STAT3/MMP2 pathway.

Currently, the commercial fixed-combination of two agents is facing several clinical challenges, including suboptimal intraocular pressure (IOP) reduction, which requires multiple daily administrations, compromised bioavailability due to rapid tear film clearance and nasolacrimal drainage, and preservative-induced ocular surface toxicity. To address these limitations, we intend to develop a novel preservative-free, long-acting fixed-combination formulation of carteolol hydrochloride and netarsudil dimesylate. This once-daily formulation demonstrates enhanced therapeutic potential through optimized physicochemical stability and extended ocular residence time in theory. However, commercialized netarsudil dimesylate is precipitated when the pH of the solution is above 5.4 or when carteolol hydrochloride is mixed with netarsudil dimesylate. Consequently, the preservative-free and long-acting fixed-combination carteolol-netarsudil containing hydroxypropyl methylcellulose (HPMC) as a thickener (FC-CN-TKN) was prepared in a pH about 5.0 solution using an extremely simple one-pot pH-adjusting solubilization strategy, achieving stable co-solubilization of both active pharmaceutical ingredients. The optimized FC-CN-TKN formulation demonstrated excellent physicochemical stability under refrigerated storage conditions. Additionally, FC-CN exerted no influence on the intraocular penetration of each active compound in the pharmacokinetic study, and HPMC-mediated viscosity enhancement significantly prolonged precorneal retention, further improving its residence time and bioavailability. Importantly, once daily, FC-CN-TKN exerted a potent IOP-lowering effect and protective effect on retinal ganglion cells. The innovative FC-CN-TKN was stable, safe, and effective, being a promising glaucoma therapy.

Propranolol hydrochloride (PRO-HCl), a nonselective β-adrenergic receptor blocker, is widely utilized in the treatment of various medical conditions including hypertension, angina pectoris, cardiac arrhythmias, migraine prophylaxis, and certain anxiety disorders. In this study, we developed a simple, convenient, and sensitive quantitative detection method for PRO-HCl in aqueous environments, based on the fluorescence generated from the reaction between Cadmium sulfide quantum dots (CdS QDs) and PRO-HCl at room temperature. The synthesized CdS QDs were thoroughly characterized using fluorescence spectroscopy, UV-Vis spectrophotometry, and Fourier-transform infrared spectroscopy (FTIR) to investigate their optical and structural properties. Our experimental results demonstrated a significant enhancement in the fluorescence intensity of CdS QDs in the presence of low concentrations of propranolol hydrochloride. Through systematic optimization of experimental conditions, we established a linear relationship between the fluorescence intensity of CdS QDs and PRO-HCl concentration within the range of 0.002-8 mg·L[-1]. The linear regression equation was determined to be Y = 0.6479X + 0.0685 with a correlation coefficient (R[2]) of 0.9858, and the detection limit was found to be 0.002 mg·L[-1]. Furthermore, we investigated the potential reaction mechanism between CdS QDs and PRO-HCl. To validate the practical application of CdS QDs, the proposed method was successfully employed for the determination of PRO-HCl in spiked environmental water samples, demonstrating the effectiveness and reliability of the CdS QDs-based detection system.

A novel spectrofluorimetric method for sensitive determination of labetalol hydrochloride was developed based on photoinduced electron transfer (PET) blocking mechanism through acidification-induced fluorescence enhancement. Upon acidification, the secondary amine functionality of labetalol undergoes protonation, resulting in five-fold fluorescence enhancement at 415-nm emission when excited at 298 nm. Quantum mechanical calculations revealed the electronic structure changes underlying the PET mechanism, with protonation causing 3.17-eV HOMO stabilization and decreased electron density on the secondary amine nitrogen that effectively eliminates electron transfer quenching. Subsequently, D-optimal experimental design systematically optimized the PET blocking conditions. The ANOVA analysis demonstrated statistical significance of the reduced two-factor interaction (2FI) model (F-value = 26.25, p < 0.0001) with satisfactory fit statistics (R[2] = 0.9459), identifying 0.6-M acetic acid, 5-min incubation time, and water-ethanol mixture as optimal conditions. The method was validated according to ICH guidelines exhibiting excellent linearity in the range of 10-300 ng/mL, detection limit of 3.23 ng/mL, and precision below 1.6% RSD. Furthermore, successful applications to pharmaceutical formulations and biological samples (plasma) demonstrated recoveries ranging from 96.36% to 104.97%. The developed PET-blocking approach provides an environmentally sustainable alternative for labetalol determination, eliminating toxic derivatization reagents while maintaining analytical reliability and sensitivity.

This overview provides a summary of the commonly used vasoactive agents and the various clinical scenarios in which they are used in the neonatal intensive care unit (NICU). The lack of well-designed clinical trials in this vulnerable population means that these agents continue to be administered without sufficient evidence-based knowledge on their dosing, safety, efficacy and long-term effects. The lack of age appropriate cardiotonic formulations remains an ongoing challenge. Future trials of cardiotonic drugs need to incorporate echocardiography and other objective monitoring tools in their design with robust assessments of short and longer-term outcomes.