Drug Database
IS

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

✓ Approved

Arbor Pharmaceuticals, LLC · CACNA1C · Small Molecule

What is isosorbide dinitrate + hydralazine?

isosorbide dinitrate + hydralazine is a small molecule developed by Arbor Pharmaceuticals, LLC. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand Nameshydralazine + ISDN, BiDil, ISDN + hydralazine
CompanyArbor Pharmaceuticals, LLC
Drug ClassSmall Molecule
Molecular TargetCACNA1C
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Arbor Pharmaceuticals, LLC

Mechanism of Action

Molecular Targets

isosorbide dinitrate + hydralazine acts on 1 molecular target:

CACNA1Ccalcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

isosorbide dinitrate + hydralazine is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Cardiac disordersCardiac failure✓ Approved

Related Research Articles

PubMedFrontiers in medicine2026-07-25

Recent progress and future perspectives of infrared light-based technology in ophthalmology.

Ding Meihua M, Sun Wei W, Lu Tailiang T, Hu Yuanyuan Y et al.

Infrared (IR) light provides non-invasive, depth-resolved imaging and diagnostic capabilities, allowing for precise tissue analysis and real-time monitoring across various applications. In recent years, IR light-based technologies-encompassing IR spectroscopy, IR imaging, IR thermography, IR eye tracking, and IR therapy-emerged as a powerful tool in ophthalmology, offering valuable insights into multiple aspects of eye health. Its ability to detect subtle changes in ocular tissues and deliver real-time data holds significant potential to enhance both diagnostic accuracy and treatment efficacy in eye care. This review highlights recent advances in the application of IR light-based technology in ophthalmology, focusing on applications such as quantitative ocular surface thermography, depth-resolved structural imaging, functional monitoring, and IR based therapeutic applications in ophthalmology. IR light's ability to penetrate ocular tissues non-invasively allows for detailed assessments of eye physiology, facilitating early disease detection and supporting personalized treatment strategies. While IR technology exhibits great potential, key challenges remain in its optimization-notably improving spectral resolution, depth penetration, and device miniaturization for expanded clinical integration. Finally, the current challenges and future prospects of IR light based-technology in ophthalmology are discussed, contributing to early diagnosis, monitoring disease progression, and evaluating treatment outcomes.

PMID 42500522
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PubMedFrontiers in endocrinology2026-07-25

Association of four non-insulin-based insulin resistance surrogate markers with colorectal cancer risk: a large-scale prospective cohort study using the UK Biobank.

Ding Ye Y, Wang Jie J, Wang Nan N, Zhu Jinyu J et al.

Colorectal cancer (CRC) remains a persistent global health challenge, with a rising incidence strongly linked to metabolic dysfunction. Insulin resistance (IR), a hallmark of metabolic dysregulation, is a well-established driver of tumorigenesis and cancer progression. However, the relative predictive value of distinct non-insulin-based surrogate markers of IR for CRC risk assessment remains poorly defined. This prospective study analyzed data from 385,206 participants in the UK Biobank. Non-insulin-based surrogate markers evaluated included the TyG index, TyG-BMI, the TG/HDL-C ratio, and METS-IR. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC. Restricted cubic splines (RCS) assessed dose-response relationships. Incremental predictive value and clinical utility were evaluated via C-index increments and decision curve analysis (DCA). Robustness was verified through extensive subgroup and sensitivity analyses. Over a median follow-up of 13.8 years, 5,175 incident CRC cases were documented. All four IR surrogates were independently and positively associated with CRC risk (all P < 0.001). In the fully adjusted model, comparing extreme quartiles (Q4 vs. Q1), the HRs (95% CIs) were 1.16 (1.07-1.26) for the TyG index, 1.20 (1.11-1.31) for TyG-BMI, 1.09 (1.01-1.19) for the TG/HDL-C ratio, and 1.21 (1.11-1.32) for METS-IR. RCS revealed significant non-linear relationships for the TyG index and METS-IR, whereas linear trends were observed for the remaining markers in the fully adjusted model. Notably, adding METS-IR and TyG-BMI to the base model yielded the most significant improvements in discrimination (both C-index increments = 0.0015; P < 0.001). Furthermore, DCA confirmed sustained net clinical benefits across practical thresholds. Subgroup analyses revealed significant interactions between the IR surrogate markers and age, sex, and smoking status (P-interaction ≤ 0.05). Multiple sensitivity analyses, including excluding cases diagnosed within the first two years, confirmed the findings' robustness. Elevated non-insulin-based IR surrogates are robust predictors of CRC risk. The BMI-integrated indices, METS-IR and TyG-BMI, demonstrated superior risk stratification performance. These low-cost, readily available tools may facilitate the early identification of high-risk individuals and inform evidence-based primary prevention strategies.

PMID 42500127
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PubMedOrthopaedic journal of sports medicine2026-07-25

The Epidemiology of Catastrophic Head and Neck Injuries in High School and College Non-Football Sports: A 4-Decade Review.

Meyer Courtney M CM, Kucera Kristen L KL, Scarneo-Miller Samantha E SE, Winkelmann Zachary K ZK et al.

Catastrophic head and neck injuries (CHNIs) in sport are rare but can have disabling or fatal outcomes. Prior studies have focused on football, equipment-laden sports, or different injury severities, not CHNI in nonfootball sports. To describe the epidemiology of CHNI across levels (high school vs collegiate) in nonfootball sports and evaluate differences in injury rates (IRs) by sport, sex, and decade. Descriptive epidemiological study. This study utilized 40 academic years (1982-1983 to 2021-2022) of surveillance data from the National Center for Catastrophic Sports Injury Research. Descriptive statistics summarized athlete, event, and injury characteristics. IRs were calculated from available institutional participation data for high school and collegiate levels. Athlete-exposure was defined as 1 athlete participating in 1 sport season. IRs per 100,000 athlete seasons (AS), IR ratios (IRRs), and 95% CIs were computed using negative binomial regression. A total of 470 eligible CHNI events were included, capturing 17 unique sports. Most injuries transpired in those who were male (69.4%; n = 326), ranged in age from 12 to 25, and competed at the high school level (76.2%; n = 358). Of injuries, 12.6% were fatal (n = 59), 38.7% were permanently disabling (n = 182), and 44.9% were temporarily disabling (n = 211). Of all male patients (n = 326), traumatic brain injury (33.4%; n = 109) and spinal fractures (34.1%; n = 111/326) were reported most frequently, while traumatic injuries (n = 144) including brain (34.0%; n = 49) and other traumatic injuries (ie, nerve injury, facial fractures, etc [30.6%; n = 44]) occurred most frequently in female patients. CHNI occurred at a lower rate in female than male patients (IR, 0.12 vs 0.48 per 100,000 AS; IRR, 0.25; 95% CI, 0.18-0.33; P < .001) and in collegiate than high school athletes (IR, 0.11 vs 0.53 per 100,000 AS; IRR, 0.20; 95% CI, 0.15-0.27; P < .001). Sports with the highest CHNI rates included gymnastics (IR, 1.66) and ice hockey (IR, 1.52). Rates declined each decade, with the largest difference in rate occurring between 1982 and 1992 (IR, 0.59; IRR, 8.93; 95% CI, 2.23-35.68) and between 2012 and 2022 (IR, 0.06). CHNI rates in nonfootball sports declined over 4 decades and were higher among athletes who were male, competing at the high school level, or participating in gymnastics or ice hockey. Over half of the athletes sustaining CHNI experienced outcomes of permanent disability or fatality.

PMID 42499583
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PubMedFrontiers in nutrition2026-07-25

Glucose-lipid metabolic dysregulation and sleep fragmentation in obstructive sleep apnea: insights from a large-scale cross-sectional study and exploratory hypoxia-related single-nucleus transcriptomic analysis.

Wei Zhicheng Z, Lu Cheng C, He Jingchun J, Huai De et al.

Sleep fragmentation impairs health and quality of life, yet its relationship with glucose-lipid metabolic dysregulation remains unclear. This study investigated this association in obstructive sleep apnea (OSA), with a focus on nocturnal hypoxia and hypoxia-related brainstem cellular responses. This large-scale cross-sectional study included 5,885 adults with suspected OSA from the Shanghai Sleep Health Study. Glucose-lipid metabolic status was assessed using the triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), metabolic score for insulin resistance (METS-IR), and metabolic syndrome. Sleep fragmentation was quantified by the micro-arousal index (MAI). Multivariable regression, restricted cubic spline, threshold effect, multiplicative and additive interaction, stratified analyses, Benjamini-Hochberg false discovery rate (FDR) correction were performed. GEO single-nucleus analyses were conducted to explore intermittent hypoxia-related cellular and metabolic pathway responses in the brainstem (metabolic activity scoring, GSVA, scTenifoldKnk). TyG, TyG-BMI, and METS-IR were independently positively associated with MAI. Each 1-unit increase in TyG was associated with a 4.0-unit increase in MAI (β = 4.0, p < 0.001). TyG-BMI and METS-IR showed significant nonlinear dose-response relationships with thresholds at 310.31 and 57.25, respectively. OSA severity and nocturnal hypoxia significantly strengthened these associations through both multiplicative and additive interactions. When AHI > 5, the associations of TyG (β = 4.04), TyG-BMI (β = 0.08), and METS-IR (β = 0.41) on MAI were more pronounced. Combined exposure was associated with 4.07-5.91-fold higher odds of elevated MAI. All primary associations remained significant after FDR correction. Single-nucleus analyses suggested widespread glucose-lipid metabolic reprogramming in brainstem cells, particularly neurons and oligodendrocytes. Glucose-lipid metabolic abnormalities were significantly associated with OSA-related sleep fragmentation, and these associations were stronger among participants with greater OSA severity and nocturnal hypoxia.

PMID 42500234
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PubMedMicrosystems & nanoengineering2026-07-25

Ultralight infrared-controlled wireless neuromodulation systems for freely behaving mice.

Cha Hyeonggyeong H, Hong Yeonghwa Y, Kim Giheon G, Lee Haeyun H et al.

Neuromodulation techniques including transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) have been widely investigated for their therapeutic potential in a range of neurological and psychiatric disorders. Basic studies using freely behaving animal models are critical for elucidating the underlying mechanisms of these neuromodulation techniques. However, conventional neuromodulation systems typically rely on wired connections or wireless systems incorporating communication and control modules, which increase device weight and volume, restrict natural behavior, and may introduce confounding factors in behavioral experiments. Here, we present an ultra-lightweight wireless neuromodulation system that can be externally controlled using infrared (IR) light, eliminating the need for complex wireless communication modules. The system incorporates wavelength-selective phototransistors (810 and 950 nm) to enable independent control of tDCS and DBS. The complete tDCS device weighs less than 1.5 g, while the DBS device weighs less than 0.5 g. Characterization of the IR LED array demonstrated uniform light distribution and high thermal stability, with no detectable temperature changes in the experimental environment during prolonged illumination. Open-field behavioral testing confirmed that neither device attachment nor IR illumination affected spontaneous locomotor activity in mice. In stimulation experiments targeting the secondary motor cortex (M2), both tDCS and DBS induced robust circling behavior in freely behaving mice, demonstrating effective modulation of motor-related neural circuits. These results indicate that the proposed systems enable reliable and selective neuromodulation without constraining natural behavior, providing a versatile platform for future behavioral and mechanistic studies of neuromodulation.

PMID 42498728
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PubMedMolecular and cellular endocrinology2026-07-25

Gut Microbiota Contributes to Protection Against High-Fat Diet- Induced Insulin Resistance in iNOS Knockout Mice.

Zanotto Tamires M TM, Santos Andrey A, Vecina Juliana F JF, Quaresma Paula G F PGF et al.

Inducible nitric oxide synthase (iNOS) is activated in obesity and is involved in the regulation of cellular pathways, including the unfolded protein response and insulin signaling. We previously showed that iNOS deficiency is associated with reduced obesity-induced insulin resistance (IR), particularly in skeletal muscle, in iNOS knockout (iNOS KO) mice fed a high-fat diet (HFD). However, the mechanisms underlying protection against HFD-induced IR in iNOS KO mice remain incompletely understood. Several studies have reported associations between gut microbiota composition and metabolic outcomes, including body weight regulation and insulin resistance, with differences observed between lean and obese subjects. However, the potential contribution of the gut microbiota to the metabolic phenotype observed in iNOS KO mice has not been fully investigated. To address this question, we assessed glucose homeostasis, adipose tissue inflammation, gut microbiota composition, and intestinal barrier integrity. Fecal microbiota transfer (FMT) experiments were also performed between HFD-fed iNOS KO and C57BL/6J mice in both directions. HFD-fed iNOS KO mice exhibited reduced adipose tissue inflammation, characterized by decreased numbers of mast cells and pro-inflammatory M1 macrophages, together with increased numbers of anti-inflammatory M2 macrophages, compared with HFD-fed C57BL/6J mice. The gut microbiota profile of HFD-fed iNOS KO mice was associated with increased expression of genes related to intestinal tight junction integrity. Fecal microbiota transfer from HFD-fed iNOS KO mice was associated with improved glucose tolerance, enhanced insulin sensitivity, and increased expression of genes related to intestinal tight junction integrity in recipient mice. These findings suggest that gut microbiota contributes, at least in part, to the protection against HFD-induced IR in iNOS KO mice and support the potential of targeting gut microbiota as a therapeutic strategy to improve metabolic disturbances.

PMID 42498211
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