amiloride hydrochloride / Generic mfg. - LARVOL DELTA

Comparative Efficacy of Aldosterone-Related Sodium-Retention Pathway Therapies for Resistant Hypertension: A Drug-Level Network Meta-Analysis of Randomized Controlled Trials. (PubMed, J Clin Hypertens (Greenwich)) - "In the primary drug-level analysis, amiloride, spironolactone, baxdrostat, eplerenone, and lorundrostat significantly reduced office systolic BP compared with placebo, with mean differences (MDs) of -14.08, -10.78, -9.09, -8.14, and -6.80 mmHg, respectively. Osilodrostat showed a statistically uncertain effect, with an MD of -2.61 mmHg...MRAs remain the established reference add-on therapy, whereas newer ASIs and amiloride may represent pathway-based alternatives for selected patients. Trial Registration: INPLASY202670099."

Clinical • Journal • Retrospective data • Cardiovascular • Hypertension

Amiloride mitigates respiratory distress caused by WFDC2 deficiency via inhibiting the epithelial sodium channel. (PubMed, Nat Commun) - "In conclusion, the p.C97W variant in WFDC2 is a critical genetic factor in severe chronic airway disease that shares clinical features with CF and PCD. Given its implications for diagnosis and treatment, genetic testing for WFDC2 mutations in individuals with CF- or PCD-like symptoms is recommended."

Journal • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis • PRSS8

The functional brake: how the epithelial ion transport network restricts CFTR efficacy in health and disease (NACFC 2026) - "We identified a marked upregulation in the amiloride-sensitive ENaC subunits SCNN1B and SCNN1G, promoting robust sodium hyperabsorption... These findings indicate that an unfavorable ENaC/SLC26A9 expression functions as a physiological brake, restricting airway hydration even when CFTR is present. This network imbalance, potentially compounded by intrinsic bottlenecks in CFTR activation or membrane stability, offers a mechanistic explanation for the baseline variability in non-CF populations and the variable efficacy of modulators in pwCF. Furthermore, it underscores that restoring CFTR function alone may fall short, positioning SLC26A9 and specific ENaC subunits as essential co-targets to fully restore airway hydration."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • CFTR • SLC26A4

Lung perfusion regulates CFTR-dependent liquid transport in live lung alveoli (NACFC 2026) - "In separate experiments, pretreatment of the alveolar epithelium with CFTRinh172 and amiloride indicated that while both alveolar liquid secretion and absorption were CFTR-dependent, only alveolar liquid absorption was ENaC-dependent... Our findings show that lung perfusion critically determines the direction of liquid transport in live alveoli of intact, perfused lungs. Specifically, lung perfusion at or near physiological PAP led to CFTR-dependent alveolar liquid secretion, whereas perfusion discontinuation or reduction to PAP below the physiological range stimulated ENaC- and CFTR-dependent alveolar liquid absorption. These data show alveoli dynamically regulate liquid transport in response to mechanical cues in the alveolar microenvironment."

Pulmonary Disease • Respiratory Diseases

Cftr in mouse secretory cells is important for coordinating chloride and fluid secretion (NACFC 2026) - "Half of the cultures were treated with 4-hydroxytamoxifen (4-OHT) from day 21 to day 28 to induce conditional secretory cell-specific Cftr deletion ( Cftr -cKO), while the remaining cultures received vehicle. Collectively, our findings demonstrate that conditional deletion of Cftr in secretory cells disrupts anion secretion, ASL homeostasis, and mucociliary function while also altering ion transport dynamics under specific conditions."

Preclinical • SCGB1A1

Hyperglycemia-conditioned macrophages induce BK channel dysfunction in airway epithelial cells (NACFC 2026) - "BKdependent short-circuit currents (Isc) were measured in Ussing chambers following ATP stimulation in the presence of amiloride... These findings demonstrate that hyperglycemia-conditioned macrophages are sufficient to induce airway inflammation and inhibit BK channel function independent of direct epithelial glucose exposure. This immune-epithelial axis may represent an important mechanism contributing to impaired ion channel function and reduced MCC in hyperglycemic states, including CF-related diabetes."

Cystic Fibrosis • Diabetes • Genetic Disorders • Immunology • Inflammation • Metabolic Disorders • Respiratory Diseases • CXCL8

Pulmonary Ionocytes Facilitate Active Chloride Secretion via CFTR in the Proximal Airway (NACFC 2026) - " We generated ionocyte CFTR conditional knock-in ( CFTR -cKI) airway liquid interface (ALI) cultures from FOXI1 -CreERT2:: CFTREGFP(lsl)/G551D ferrets, in which CFTR can be reactivated in ionocytes upon exposure to 4- hydroxytamoxifen (OH-TAM) in the context of CF...CFTR -cKI specifically within ionocytes significantly increased airway organoid swelling in the presence of forskolin and amiloride as compared to CF. Reactivation of a single allelic CFTR within ionocytes effectively restores the defective Cl- secretion in CF. Ionocyte CFTR mediates active Cl- transport under native transepithelial voltage conditions, thereby contributing to airway fluid secretion."

CFTR Restoration by Gene-Edited Airway Stem Cells Transplanted After Mechanical Airway Preconditioning (NACFC 2026) - "Gene corrected ABCs retain their ability to engraft, undergo multi-lineage differentiation and restore CFTR function when transplanted after LAMP. Notably, LAMP may enable replacement of CF airway cells in upto 4 generations of bronchi without damaging the alveoli. These findings support the development of autologous gene edited airway stem cell therapy for all pwCF."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • Transplantation • CD19 • KRT5 • KRT7 • SCGB1A1

ASIC currents in cultured primate retinal rod and cone cells. (PubMed, Pflugers Arch) - "The currents were almost completely blocked by amiloride and highly sensitive to PcTx-1. Our results for the first time demonstrate the expression of functional ASICs on primate photoreceptors and suggest that ASIC currents in these cells are mediated predominantly by homomeric ASIC1a channels."

Journal • Metabolic Disorders

Comparative Effectiveness of Chlorthalidone Versus Hydrochlorothiazide and Dose-Response of Amiloride on Blood Pressure and Biochemical Parameters. (PubMed, J Am Heart Assoc) - P3 | "Chlorthalidone and hydrochlorothiazide, administered at a 1:2 dosing ratio, show similar effects on BP and laboratory parameters. Amiloride 5 and 10 mg show similar effects on BP and most metabolic parameters, with no clear dose-response relationship, suggesting that any independent BP-lowering effect of amiloride is, at best, weak."

Clinical • HEOR • Journal • Cardiovascular • Hypertension • Hypotension

Development of a rapid antiviral screening assay based on GFP reporter virus of bovine enterovirus. (PubMed, Arch Virol) - "Using this system, we found that 5-(N-Ethyl-N-isopropyl)amiloride (EIPA) inhibited BEV replication, suggesting its potential as an antiviral candidate. Overall, the rHB19-GFP infectious clone developed here offers a practical tool for studying BEV biology and for identifying antiviral compounds against BEV."

Journal • Preclinical • Cytomegalovirus Infection

Acid Sensing Ion Channels (ASICs) in the brain: emerging roles in physiology and pathology. (PubMed, Pflugers Arch) - "ASICs belong to the epithelial sodium channel/degenerin (ENaC/DEG) family of amiloride-sensitive transmembrane ion channel proteins...Here we shall focus on brain ASICs in the context of the following issues. (i) The role of ASICs in the homeostasis of extracellular рН in the brain; (ii) interactions of ASICs with major neurotransmitters and (iii) ASICs as emerging key factors and drug targets in brain pathology with focus on stroke, neurological consequences of neonatal hyperbilirubinemia, and Alzheimer's disease."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders

Aldosterone-renin ratio and plasma renin activity as biomarkers for treatment response in resistant hypertension. (PubMed, Hypertens Res) - "A recent randomised trial demonstrated the non-inferiority of amiloride versus spironolactone in resistant hypertension, with exploratory analyses suggesting heterogeneity in treatment response based on baseline aldosterone-renin ratio (ARR). No significant between-drug difference was efficacy regardless of renin-aldosterone profile. No significant between-drug difference was observed within individual strata."

Biomarker • Journal • Cardiovascular • Hypertension

Macropinocytosis inhibition attenuates fibroblast activation and bleomycin-induced skin fibrosis. (PubMed, J Invest Dermatol) - No abstract available

Journal • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

Upregulated Renal Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 2 Are Associated with K+ Retention During MR Antagonism in Female Spontaneously Hypertensive Rats. (PubMed, Int J Mol Sci) - "Higher serum K+ levels in spironolactone-treated female SHRs were accompanied by transiently reduced urinary K+ excretion and a fourfold increase in aldosterone at the study's end...MR antagonism did not alter ENaC activity, α-ENaC protein abundance, blood pressure, or amiloride-sensitive urinary electrolyte excretion in either sex. Collectively, the upregulation of renal MR and 11β-HSD2 in females was associated with elevated circulating potassium in response to MR blockade, an effect that was likely counterbalanced by a compensatory rise in aldosterone. Low renin-angiotensin-aldosterone system activity in SHRs may limit the antihypertensive efficacy of MR antagonists."

Journal • Preclinical • Cardiovascular • Hypertension

Renal TRPM6 but not Kv1.1 is required for magnesium homeostasis in mice. (PubMed, Am J Physiol Renal Physiol) - "GFR, lithium clearance, and natriuretic responses to furosemide, hydrochlorothiazide, or amiloride did not differ in tubule-Kv1.1 KO mice. In summary, renal TRPM6 plays a critical role in magnesium homeostasis under baseline conditions. Kv1.1 is not expressed along DCT and is not required for magnesium homeostasis or normal renal function at baseline."

Journal • Preclinical • Nephrology • Renal Disease • DCT

Nephrogenic Diabetes Insipidus Presenting with Hypokalemic Paralysis in an Adolescent with Primary Sjögren's Syndrome: A Case Report. (PubMed, Kidney Blood Press Res) - "This case highlights the pathophysiologic cascade of pSS-related dRTA causing secondary NDI and underscores the importance of early recognition and tailored diuretic selection in adolescents."

Journal • Immunology • Metabolic Disorders • Nephrology • Pediatrics • Rare Diseases • Sjogren's Syndrome

Dissociation between amiloride-sensitive taste responses and ingestive behavior to sodium ascorbate in osteogenic disorder Shionogi rats. (PubMed, Chem Senses) - "Instead, intake is likely influenced by post-ingestive mechanisms in a concentration- and state-dependent manner. These findings suggest an important contribution of internal nutritional signals in shaping chemosensory-driven behavior."

Journal • Preclinical

Pregnancy, primary aldosteronism and renal tubular disorders: a case-based lesson and review of the utility of amiloride. (PubMed, J Nephrol) - No abstract available

Journal • Cardiovascular • Endocrine Disorders • Hypertension

Abnormal activation of the mineralocorticoid receptor in the aldosterone-sensitive distal nephron contributes to fructose-induced salt-sensitive hypertension. (PubMed, Am J Physiol Renal Physiol) - "FHS also increased BP by 23±6 mmHg compared to GHS, and blocking MRs with eplerenone prevented this increase. Additionally, inhibiting ENaC with amiloride significantly reduced BP in FHS from 148±6 to 134±5 mmHg (p≤0.019)...FHS did not change β- or γ-subunit expression. These results suggest that fructose-induced salt-sensitive hypertension depends, in part, on abnormal Na+ retention by ENaC, resulting from the activation of MRs by glucocorticoids."

Journal • Cardiovascular • Hypertension

Liddle syndrome caused by SCNN1B mutation presenting with severe early-onset hypertension and hypokalemia in an adolescent: a case report. (PubMed, BMC Endocr Disord) - "Although SCNN1B p.Pro618Arg is a recognized pathogenic hotspot variant, this case highlights the severe phenotypic consequences of delayed diagnosis in adolescents, and demonstrates that early genetic diagnosis and targeted ENaC inhibitor therapy are achievable even in resource-limited rural clinical settings. Early recognition and targeted therapy with ENaC inhibitors are critical to prevent serious cardiovascular and cerebrovascular complications. Genetic testing is essential for definitive diagnosis, particularly in resource-limited settings where misdiagnosis as primary aldosteronism (PA) may lead to ineffective treatment."

Journal • Cardiovascular • CNS Disorders • Endocrine Disorders • Hypertension • Metabolic Disorders • Nephrology • Vascular Neurology • CYP11B1

Navigating the Therapeutic Tightrope: Refractory Lithium-Induced Nephrogenic Diabetes Insipidus in a Patient With Advanced Chronic Kidney Disease. (PubMed, Cureus) - "However, management becomes exponentially more complex when therapeutic options, such as thiazides or amiloride, are contraindicated due to advanced chronic kidney disease (CKD) or electrolyte instability. We are reporting the case of a man in his 60s with a 40-year history of lithium use who presented with acute-on-chronic kidney injury (AKI) and severe hypernatraemia (164 mmol/L) refractory to standard desmopressin therapy. This case highlights the limitations of conventional NDI treatments in the setting of a low estimated glomerular filtration rate (eGFR) and the necessity of intensive, multidisciplinary care."

Journal • Bipolar Disorder • Chronic Kidney Disease • CNS Disorders • Metabolic Disorders • Nephrology • Psychiatry • Renal Disease

Small-molecule inhibition of the Orientia tsutsugamushi deubiquitylating enzyme OtDUB impairs bacterial reproduction. (PubMed, bioRxiv) - "Two compounds, gentisic acid and amiloride hydrochloride, inhibited OtDUB activity at low dosage, with little effect on the related Wolbachia CidB or yeast Ulp1 enzymes...While the identified compounds are not optimized inhibitors, they establish that bacterial pathogen-encoded deubiquitylating enzymes can be targeted by small molecules. Overall, our results provide a framework for using selective inhibitors as tools to study DUB function in genetically intractable intracellular bacteria and as potential treatments for scrub typhus."

Journal • Infectious Disease • Targeted Protein Degradation

Neuraminidase1 Activity Contributes to Vasopressin Receptor-mediated Augmentation of Water and Electrolyte Retention by the Kidney in Eln Haploinsufficient Mice. (PubMed, bioRxiv) - "Conversely, V2R stimulation with desmopressin markedly increased urinary sodium excretion in male Eln +/+ but not Eln +/- mice, while both sexes of Eln +/- mice exhibited marked suppression of urine flow rate...NEU1 blockade strikingly enhanced the natriuretic effect of furosemide and amiloride in male Eln +/+ and modestly in Eln +/- mice...These findings reveal a novel mechanism by which abnormal ERC activity due to Eln haploinsufficiency potentially contributes to renal dysfunction and hypertension. AC, adenylyl cyclase; AQP2, aquaporin 2; CD, collecting duct; CNT, connecting tubule; DCT, distal convoluted tubule; EBP, elastin binding protein; Eln , elastin allele; ENaC, epithelial sodium channel; ERC, elastin receptor complex; Gs, stimulatory Gα subunit; NEU1, neuroaminidase1; NKCC2, sodium-potassium-chloride cotransporter; PPCA, protective protein/ cathepsin A; TAL, loop of Henle thick ascending limb; V2R, vasopressin receptor type 2."

Journal • Preclinical • Cardiovascular • Developmental Disorders • Genetic Disorders • Hypertension • Nephrology • Renal Disease • NEU1

Liddle Syndrome Presenting as Hypertensive Crisis and Myocardial Injury in a Young Male: A Case Report. (PubMed, Case Rep Nephrol) - "The diagnosis must be made promptly because delay may lead to complications. In instances where molecular testing is impractical, treatment with ENaC inhibition using amiloride is diagnostic and potentially life-saving."

Journal • Acute Coronary Syndrome • Cardiovascular • Endocrine Disorders • Genetic Disorders • Hypertension • Metabolic Disorders • Nephrology • Pain