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isosorbide dinitrate + hydralazine (hydralazine + ISDN / BiDil / ISDN + hydralazine)

✓ Approved

Arbor Pharmaceuticals, LLC · CACNA1C · 小分子

什么是 isosorbide dinitrate + hydralazine？

isosorbide dinitrate + hydralazine 是一种小分子，由Arbor Pharmaceuticals, LLC研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名hydralazine + ISDN, BiDil, ISDN + hydralazine
公司Arbor Pharmaceuticals, LLC
药物类别小分子
分子靶点CACNA1C
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Arbor Pharmaceuticals, LLC

作用机制

分子靶点

isosorbide dinitrate + hydralazine 作用于 1 个分子靶点：

CACNA1Ccalcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

isosorbide dinitrate + hydralazine 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Cardiac disordersCardiac failure✓ Approved

相关研究文献

PubMedMedical sciences (Basel, Switzerland)2026-07-27

Valve-Related Outcomes up to Six Years of a Next-Generation Bovine Pericardial Bioprosthesis Compared with Its Predecessor: A Propensity-Matched Analysis.

Francica Alessandra A, Perrone Fabiola F, Maffei Irene I, Denora Maria Teresa MT et al.

Background: Current ESC/EACTS guidelines recommend bioprosthetic valves for aortic valve replacement (AVR) in patients > 65 years, yet their use is increasing among younger individuals. The INSPIRIS Resilia (IR) valve, a next-generation bioprosthesis, was designed to improve durability and reduce structural valve degeneration (SVD). This study compares clinical and valve-related outcomes up to six years in patients undergoing AVR with either the IR or its predecessor, the Perimount Magna Ease (PME) valve. Methods: Between January 2017 and December 2023, 2053 patients underwent isolated or combined AVR at a single institution (1602 PME; 451 IR). Propensity-score matching identified 224 patient pairs with comparable baseline characteristics. Outcomes were assessed over follow-up extending up to six years, focusing on cardiovascular and valve-related adverse events. Transvalvular gradients were also assessed at follow-up. Results: After matching, mean age was 64.2 ± 7.7 years in both groups. Freedom from cardiovascular mortality at six years was similar between PME and IR (96.6% vs. 98.2%; p = 0.34), as were rates of stroke, rehospitalization, prosthetic valve endocarditis, and reintervention. A total of 12 PME (5.4%) and six IR valves (2.5%) were explanted during follow-up (p = 0.15), with prosthetic endocarditis representing the leading cause of reintervention. Only one case of severe SVD was observed in both groups. Conclusions: In patients undergoing AVR with comparable baseline risk profiles, IR and PME valves demonstrated similar clinical, valve-related, and hemodynamic outcomes up to six years of follow-up. Prosthetic valve endocarditis represented the leading cause of valve failure, whereas structural valve deterioration remained rare. Longer follow-up and a greater number of valve-related events will be necessary to determine whether differences in bioprosthetic valve degeneration emerge over time.

PMID 42506380
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PubMedEpidemiology and psychiatric sciences2026-07-27

Adverse childhood experiences and adolescent mental health: trajectories of internalizing, externalizing and prosocial behaviour in a longitudinal cohort study.

Charan Iftikhar Ahmed IA, Chongjin Wang W, Soomro Shazia S

Adverse childhood experiences (ACEs) shape children's socioemotional development, yet longitudinal evidence from low- and middle-income countries remains limited. This study examined how ACEs relate to internalizing, externalizing and prosocial behaviours from childhood to adolescence in a rural Pakistani cohort. Data were drawn from the Bachpan Cohort, a longitudinal study including 1,791 observations across three waves: ages 4-5, 8-9 and 12-15 years. ACEs were assessed using an adapted ACE-International Questionnaire. Outcomes were measured using the Strengths and Difficulties Questionnaire. Network analysis, dose-response modelling and moderation analyses were employed. Emotional neglect was the most prevalent ACE (83.7%). Parental psychiatric issues, parental trauma exposure and emotional neglect were the most central ACE stressors. A dose-response relationship emerged: compared to children with no ACEs, those with four or more ACEs showed higher internalizing (incidence ratio [IR] = 4.24) and externalizing problems (IR = 3.42) and lower prosocial behaviour (IR = 0.90). Girls showed greater internalizing vulnerability; boys showed more externalizing problems. ACE effects on internalizing problems strengthened with age. ACEs are strongly associated with internalizing, externalizing and prosocial outcomes from childhood to adolescence. Findings highlight the need for tiered, gender-sensitive and developmentally appropriate interventions in low-resource settings.

PMID 42503645
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PubMedNano letters2026-07-27

Lanthanide Doping and Dual-Site Switching on Amorphous High-Entropy Metallene Oxides Boost Acidic Water Oxidation.

Li Yinghao Y, Sun Yuntong Y, Chen Mengshan M, Zhou Yingtang Y et al.

High-entropy oxides (HEOs) are promising electrocatalysts for breaking the Sabatier principle and maximizing their oxygen evolution reaction (OER) efficiency. Herein, the effect of lanthanide doping on RuIr-based HEOs is investigated through theoretical and experimental studies. The optimized amorphous RuIrMnCoGd high-entropy metallene oxides (a-Gd_HEMOs) with moderate intermediate affinity exhibit a small overpotential of 211 mV and an ultralong stability of 700 h at 10 mA cm-2 in acidic media. Integrated into a proton exchange membrane electrolyzer, they deliver 3.0 A cm-2 at 1.872 V and maintain stable operation for 300 h at 1.0 A cm-2. Operando characterizations reveal the changes in electronic configurations and coordination environments of Ru and Ir sites during OER. Theoretical simulations further clarify the adsorbate evolution mechanism and the distinct role of the constituent elements. Specifically, the switching of Ru and activated Ir as primary active sites at low and high potentials, respectively, enhances robustness for oxygen generation.

PMID 42503705
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PubMedThe journal of physical chemistry. A2026-07-27

Assessing Constrained Nuclear-Electronic Orbital Theory for the Floppy CH5+ Ion: Geometry-Dependent Zero-Point Effects on Structure, Hydrogen Rearrangement Dynamics, and Simulated IR Spectra.

Wang Yiwen Y, Chen Zehua Z, Zhang Yuzhe Y, Sibert Edwin L EL et al.

Recently, constrained nuclear-electronic orbital (CNEO) theory has been developed to incorporate nuclear quantum delocalization and zero-point effects into quantum chemistry calculations and ab initio molecular simulations. Motivated by discussions with John Stanton, we apply CNEO methods to protonated methane, CH5+, as a stringent test case for the quantum-corrected effective-potential framework. CH5+ is a prototypical penta-coordinated nonclassical carbonium ion with a highly anharmonic potential energy surface, many low-lying geometries connected by low barriers, and extensive fluxional motion. Using CNEO, we examine the effective structural features, hydrogen rearrangement dynamics, and simulated IR spectra of CH5+. The CNEO effective potential energy surface exhibits a minimum with C2v symmetry, which is more symmetric than the minimum-energy eclipsed-Cs structure on the conventional potential energy surface. CNEO molecular dynamics predicts more frequent hydrogen rearrangement than conventional ab initio molecular dynamics, with pronounced rearrangement observed starting from 50 K. A Fourier-filtered analysis of C-H bond-length distributions along the trajectories, combined with a Gaussian mixture model, reveals three structural and dynamical motifs: equilibrium-like, fluxional, and transition-state hovering configurations. The simulated IR spectra, which are obtained from either harmonic analysis or classical dynamics on the CNEO surface, are compared qualitatively with experimentally observed spectral features. Overall, this work assesses how the computationally efficient CNEO framework captures qualitative structural, dynamical, and spectroscopic trends in the highly fluxional CH5+, while also highlighting the challenges and shortcomings of this classical-trajectory-based method in a system where fully quantum nuclear effects beyond zero-point effects are important.

PMID 42505003
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PubMedMetabolites2026-07-27

Urinary Albumin-to-Creatinine Ratio Across Phenotypes of Polycystic Ovary Syndrome: A Phenotype-Based Evaluation.

Oner Oznur O, Akkus Canan C, Demircioglu Doga D, Karanlık Ilhan I et al.

Background/Aim: Albuminuria is a clinical marker associated with microvascular involvement and an independent predictor of cardiovascular risk. Polycystic ovary syndrome (PCOS) is associated with early metabolic and vascular abnormalities; however, whether albumin excretion differs across PCOS phenotypes remains unclear. This study aimed to evaluate the urinary albumin-to-creatinine ratio (U-ACR) across PCOS phenotypes and to examine its association with metabolic parameters. Materials and Methods: In this cross-sectional study, 180 women aged 18-35 years with PCOS and 51 age-matched healthy controls were included. PCOS phenotypes were classified according to the Rotterdam criteria as Phenotype A (n = 96), Phenotype B (n = 19), Phenotype C (n = 35), and Phenotype D (n = 30). Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-IR). Urinary albumin and creatinine levels were measured in morning urine samples, and U-ACR was calculated. Results: Age was comparable across all groups. Body mass index, waist circumference, diastolic blood pressure, and HOMA-IR were significantly higher in Phenotype A compared with controls and other phenotypes, reflecting a more adverse metabolic profile. Serum creatinine levels were similar across all groups. Despite this metabolic profile in Phenotype A, U-ACR was significantly elevated only in Phenotype B compared with controls (p = 0.018), and Phenotype D (p = 0.016). No significant correlations were observed between U-ACR and age, body mass index, or HOMA-IR. When participants were categorized according to U-ACR levels (<30, 30-299.9, and ≥300 mg/g creatinine), no significant differences in category distribution were observed between the total PCOS cohort, phenotype subgroups, and controls. Conclusion: Among PCOS phenotypes, U-ACR elevation was observed exclusively in Phenotype B despite similar renal function markers. This finding, in the presence of a more adverse metabolic profile in Phenotype A, suggests a dissociation between metabolic burden and early microvascular involvement across PCOS phenotypes. These findings suggest a potential phenotype-specific pattern that warrants further investigation.

PMID 42506402
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PubMedThe journal of physical chemistry letters2026-07-27

Size-Selective CO2 Activation by Vanadium-Doped Cobalt Clusters.

Pradeep Deepak D, Yusti Barbara Zamora BZ, Zijlstra Rutger T RT, Szalay Mate M et al.

CO2 activation is the primary step for CO2 reduction to C2 products. To understand the reactivity of bimetallic catalysts toward CO2 and, in particular, the role of dopant elements, we experimentally studied CO2 adsorption on pure and vanadium-doped cationic cobalt clusters. Doped and pristine clusters are reacted with CO2 in a flow tube-like reaction channel, and resulting cluster-CO2 products are characterized by free-electron laser-based infrared (IR) spectroscopy. The spectra for CO2 adsorbed on pure Con+ clusters are highly similar for each cluster size studied, and they indicate that CO2 is mostly physisorbed on the cluster. However, substituting a Co atom with a single V atom results in strongly varying IR spectra for VCon-1+·CO2 adducts, indicative for size-selective activation, dissociation, and even cluster oxidation. An absolute localized molecular orbital-based energy-decomposition analysis and decomposition into complementary occupied-virtual pairs reveals that charge transfer from the cluster into the CO2 antibonding π* lowest unoccupied molecular orbital is the dominant factor in activation, combined with an overall more positive charge on the vanadium atom and a strong dative V-O bond in the dissociated product. The size selectivity demonstrates how a fine interplay between dopant element and cluster size could be made instrumental in tuning the reactivity of catalyst materials.

PMID 42503826
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