rimeporide (EMD 87580) / EspeRare - LARVOL DELTA

Inhibition of Sodium/Hydrogen Exchanger-1 in the Right Ventricle and Lung Dysfunction Induced by Experimental Pulmonary Arterial Hypertension in Rats. (PubMed, J Am Heart Assoc) - "By specifically inhibiting NHE-1, rimeporide at the selected dosage revealed remarkable anti-PAH effects by preventing the functional, morphological, and biochemical deleterious effects of PAH on the right ventricle and lungs. Rimeporide should be considered as a potential treatment for PAH."

Journal • Preclinical • Cardiovascular • Fibrosis • Heart Failure • Hypertension • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Early Cardiac Dysfunction in Duchenne Muscular Dystrophy: A Case Report and Literature Update. (PubMed, Int J Mol Sci) - "This case report presents a rare instance of early-onset cardiac involvement in a 3-year-old male with a confirmed deletion in exon 55 of the dystrophin gene...Genetic mechanisms and genotype-phenotype correlations related to cardiac involvement were reviewed, highlighting emerging therapies such as exon skipping, vamorolone, ifetroban, and rimeporide...While current DMD care standards improve survival, optimizing management through early intervention and novel therapies remains essential. Further research is needed to better understand genotype-phenotype correlations and improve cardiac outcomes for patients with DMD."

Journal • Review • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Genetic Disorders • Heart Failure • Muscular Dystrophy

Small Molecules for the Treatment of Long-COVID-Related Vascular Damage and Abnormal Blood Clotting: A Patent-Based Appraisal. (PubMed, Viruses) - "Treatments for COVID-19 include antiplatelet (e.g., aspirin, clopidogrel) and anticoagulant agents, but their impact on morbidity and mortality has not been proven. By retrieving patent literature published in the last two years, small molecules patented for long-COVID-related blood clotting and hematological complications are herein examined, along with supporting evidence from preclinical and clinical studies. An overview of the main features and therapeutic potentials of small molecules is provided for the thromboxane receptor antagonist ramatroban, the pan-caspase inhibitor emricasan, and the sodium-hydrogen antiporter 1 (NHE-1) inhibitor rimeporide, as well as natural polyphenolic compounds."

Adverse events • Journal • Cardiovascular • CNS Disorders • Coronary Artery Disease • Heart Failure • Hematological Disorders • Infectious Disease • Ischemic stroke • Novel Coronavirus Disease • Thrombosis • Vascular Neurology • Venous Thromboembolism

Pharmacological Inhibition of NHE1 Protein Increases White Matter Resilience and Neurofunctional Recovery after Ischemic Stroke. (PubMed, Int J Mol Sci) - "In this study, we tested the efficacy of two potent NHE1 inhibitors, HOE642 and Rimeporide, with a delayed administration regimen starting at 24 h post-stroke in adult C57BL/6J mice. The pharmacological blockade of NHE1 protein activity reduced microglia inflammatory responses and enhanced oligodendrogenesis and white matter repair, leading to motor and cognitive function recovery after stroke. Our study reveals the potential of targeting NHE1 protein as a therapeutic strategy for ischemic stroke therapy."

Journal • Cardiovascular • Inflammation • Ischemic stroke • Solid Tumor

Exploring theinteraction of guanidine ligands amiloride, rimeporide and cariporide with DNA for understanding their role as inhibitors of Na/H exchangers (NHEs): A spectroscopic and molecular docking investigation. (PubMed, Int J Biol Macromol) - "The docked structures depicted binding energy of -6.4 kcal mol for amiloride and - 6.6 kcal mol for rimeporide and cariporide. Such physicochemical studies of DNA-ligand interactions may facilitate the understanding of the mechanisms of NHE inhibition."

Journal • Cardiovascular • CNS Disorders • Oncology

Hypotension in hereditary cardiomyopathy. (PubMed, Pflugers Arch) - "Treatments with the potent NHE1 inhibitor, EMD 87580 (rimeporide), did not affect MAP of NH...These results suggest that a decrease in blood pressure could be a biomarker signal for HCM leading to HF and early death. Since the blockade of NHE1 significantly but partially prevented the reduction in MAP, this suggests that other mechanisms can contribute to the development of hypotension in HCM."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Hypotension

Characterization of modeled inhibitory binding sites on isoform one of the Na/H exchanger. (PubMed, Biochim Biophys Acta Biomembr) - "Resistance to inhibition by EMD87580 was elevated in mutants F438A, L465A and L468A and reduced in mutants S351A, Y381A, H473A, M476A and L481A...The greatest changes in activity and inhibitor sensitivity were in mutants present in binding site B which is more closely associated with TM4 and C terminal of extracellular loop 5, and is situated between the putative scaffolding domain and transport domain. The results help define the inhibitor binding domain of the NHE1 protein and identify new amino acids involved in inhibitor binding."

Journal • Cardiovascular • Heart Failure • Oncology • F13A1

Anti-hypertrophic effect of Na/H exchanger-1 inhibition is mediated by reduced cathepsin B. (PubMed, Eur J Pharmacol) - "H9c2 cardiomyoblasts were stimulated with Angiotensin (Ang) II in the presence and absence of N-[2-methyl-4,5-bis(methylsulphonyl)-benzoyl]-guanidine, hydrochloride (EMD, EMD 87580), an NHE1 inhibitor or CA-074Me, a Cat B inhibitor, and various cardiac hypertrophic parameters, namely cell surface area, protein content and atrial natriuretic peptide (ANP) mRNA were analyzed...Moreover, Cat B protein expression and MMP-9 activity in the extracellular space were significantly attenuated in the presence of EMD or CA-074Me. Our study demonstrates a novel mechanism for attenuation of the hypertrophic phenotype by NHE1 inhibition that is mediated by a regression in Cat B. The inhibition of Cat B via EMD or CA-074Me attenuates the autosomal-lysosomal pathway and MMP-9 activation."

Journal • CTSB • MMP9

Rimeporide as a first- in-class NHE-1 inhibitor: Results of a phase Ib trial in young patients with Duchenne Muscular Dystrophy. (PubMed, Pharmacol Res) - "PK evaluations showed that Rimeporide was well absorbed orally reaching pharmacological concentrations from the lowest dose, with exposure increasing linearly with dose and with no evidence of accumulation upon repeated dosing. Exploratory PD biomarkers showed positive effect upon a 4-week treatment, supporting its therapeutic potential in patients with DMD, primarily as a cardioprotective treatment, and provide rationale for further efficacy studies."

Clinical • Journal • P1 data • Cardiovascular • Congestive Heart Failure • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Heart Failure • Muscular Dystrophy

Protective effects of rimeporide on left ventricular function in golden retriever muscular dystrophy dogs. (PubMed, Int J Cardiol) - "Chronic administration of the NHE1 inhibitor rimeporide exerted a protective effect against LV function decline in GRMD dogs. This study provides proof of concept to explore the cardiac effects of rimeporide in DMD patients."

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