amiloride hydrochloride / Generic mfg. - LARVOL DELTA

ASIC currents in cultured primate retinal amacrine/ganglion cells. (PubMed, Physiol Rep) - "The currents were almost completely blocked by amiloride (100 μM) but were insensitive to PcTx-1 (20 nM). The currents were potentiated by zinc (100 μM) and showed recovery from desensitization with a time constant of 0.18 s and were resistant to low conditioning pH with a pH 0.5 for steady-state inactivation of 6.45. Our results for the first time demonstrate the expression of functional ASICs in primate amacrine/ganglion cells and suggest that ASIC currents in these cells are mediated predominantly by ASIC2a containing channels."

Journal • Metabolic Disorders

Management of drug-resistant hypertension as a heterogeneous disorder. (PubMed, Pharmacol Ther) - "Other strategies include sequential nephron block (e.g., spironolactone + furosemide + amiloride), and use of drugs such as alpha2 agonists, endothelin antagonists, and nonsteroidal mineralocorticoid antagonists. There is also ample data in literature suggesting the non-compliance to antihypertensive medications as a significant barrier to lowering blood pressure in this group. Accordingly, education regarding pharmacotherapy, and appropriate exercise regimen, including changes to diet should underpin any strategy in the management of high blood pressure in this population."

Heterogeneity • Journal • Review • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Obstructive Sleep Apnea • Renal Disease • Respiratory Diseases • Sleep Disorder

THE ROLE OF INTESTINAL PERMEABILITY AND IONIC IMBALANCES IN FLUID LOSSES IN PATIENTS WITH SHORT BOWEL SYNDROME. (DDW 2025) - "To asses ion secretion, the short-circuit current (Isc) needed to keep the PD clamped at 0 mV, was measured whereafter luminal amiloride (100 µM, a blocker of the Na + /H + exchanger) and luminal glucose (15mM, to stimulate the Na + /glucose cotransporter 1 (SGLT1)) was added, all for 10 min...The higher glucose-induced Isc indicates an increase of glucose uptake through SGLT1 in patients with SBS which may contribute to the natural intestinal adaptation after resection. Further research is needed to confirm our findings and explore the potential underlying mechanisms."

Clinical • Gastrointestinal Disorder • Short Bowel Syndrome

Automated patch-clamp recordings for detecting activators and inhibitors of the epithelial sodium channel (ENaC). (PubMed, Pflugers Arch) - "This resulted in a high success rate of APC recordings with amiloride inhibitable ENaC currents...This recovery protocol enhanced the relative stimulatory effect of chymotrypsin, a prototypical serine protease known to cause proteolytic ENaC activation. Thus, this protocol may be particularly useful for identifying novel ENaC activators mimicking proteolytic channel activation. In conclusion, we have established a high-throughput screening method for the identification of novel ENaC activators and inhibitors using APC."

Journal • Pulmonary Disease • Respiratory Diseases

Clinical case of arginine vasopressin resistance associated with a new mutation in the AVPR2 gene (ESPE-ESE 2025) - "Desmopressin therapy was initiated without clinical effect...It was decided to resume hydrochlorothiazide treatment at a reduced daily dose (25 mg) alongside potassium supplements, while a potassium-sparing diuretic (amiloride) was also introduced at a dose of 5 mg daily...Timely and accurate diagnosis not only prevents severe complications and initiates adequate treatment but also significantly enhances the patient’s quality of life. The vigilance of primary care physicians in the presence of polydipsia-polyuria syndrome, competent patient routing, and an interdisciplinary approach are crucial in diagnosing and managing patients with AVR."

Clinical • Endocrine Disorders • Rare Diseases

Severe hyponatremia due to trimethoprim-sulfamethoxazole: a case report. (PubMed, AME Case Rep) - "Trimethoprim-sulfamethoxazole (TMP-SMX) and spironolactone are two frequently administered medications; regrettably, most healthcare professionals are not aware that these medications might cause hyponatremia...Structurally akin to the potassium-sparing diuretic amiloride, TMP-SMX is linked to hyperkalemia and hyponatremia by obstructing epithelial sodium channels in the distal nephron...Thus, this report underscores the importance of vigilant monitoring and prompt identification of hyponatremia in patients undergoing TMP-SMX treatment. Further research is warranted due to limited data on the precise mechanisms of TMP-SMX-induced hyponatremia."

Journal • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Heart Failure • Hypertension • Infectious Disease • Metabolic Disorders • Type 2 Diabetes Mellitus

Integrative bioinformatics and machine learning identify key crosstalk genes and immune interactions in head and neck cancer and Hodgkin lymphoma. (PubMed, Sci Rep) - "Drug sensitivity analysis identified Andrographolide, Rituximab, and Amiloride as potential therapeutic agents. This study identified IL6, CXCL13, and PLAU as critical biomarkers involved in immune regulation and tumor progression in both HNSCC and HL. These findings provide valuable insights into the shared molecular mechanisms and suggest novel therapeutic strategies for patients affected by these diseases."

Journal • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CXCL13 • IL6 • PLAU

Don't Get Salty, Baby! A Rare Case of Geller Syndrome (ATS 2025) - "She received magnesium for maternal seizure prophylaxis and labetalol for blood pressure control...Geller syndrome was suspected and amiloride was initiated, with rapid improvement in K levels...An activating mutation in the gene that encodes MR S810L allows progesterone to bind in a similar way that aldosterone does, which leads to increased salt reabsorption in the renal sodium channels...Increased awareness of this disease in obstetrics and critical care is essential, as its risks pose a major threat to the lives of expectant mothers and their children. Consideration of screening for this genetic mutation in routine obstetric practice may be beneficial, as treatment is readily available."

Clinical • Cardiovascular • CNS Disorders • Epilepsy • Gynecology • Hypertension • Obstetrics

Impact of Common Co-morbidities on Cardiopulmonary Function and Alveolar Fluid Clearance in Mice (ATS 2025) - "AFC was quantified in live mechanically-ventilated mice by the BSA concentration method, with or without 100 μM amiloride in the instillate... Aging and obesity impair cardiopulmonary function and AFC even in the absence of any lung insult. Underlying defects in AFC may predispose elderly and obese patients to worse ARDS outcomes. and the presence of these co-morbidities should be considered when conducting clinical trials of therapeutics designed to improve AFC."

Preclinical • Acute Respiratory Distress Syndrome • Genetic Disorders • Infectious Disease • Obesity • Pneumonia • Respiratory Diseases • Septic Shock

CFTR-Mediated Ion and Fluid Transport by Primary Ferret AT2 Epithelia (ATS 2025) - "In the presence of amiloride and DIDS to inhibit ENaC and non-CFTR anion channels, respectively, IBMX/forskolin induced chloride currents by WT AT2 ALI cultures (ΔIsc 33.57 ± 9.65 µA/cm2), but not G551D cultures (ΔIsc 0.13 ± 0.69 µA/cm2)... We demonstrate the ability to propagate ferret AT2 cells and maintain them as undifferentiated epithelia in ALI and organoid cultures. chloride movement by AT2 cells facilitates salt-mediated fluid movement, which counterbalances CFTR-independent fluid absorption. The mechanisms by which these processes interact in native mixed epithelial populations containing both AT2 and AT1 cells remain to be determined."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Lower Airway Potential Difference Testing Using a Novel Integrated Image Guided System (ATS 2025) - "We then tested a freshly euthanized swine to bronchoscopically introduce the probe into the lower airways to obtain PD values after perfusion of solutions to inhibit the epithelial sodium channel, ENaC (ΔAmiloride) and activate CFTR (ΔCl-free + isoproterenol)... Use of the novel image guided LAPD probe was feasible, safe, well tolerated, provided physiologically relevant PD values, and has the potential to substantially improve the quality of measurements in a pre-manufactured system. As treatment options for CF advance to include lower airway specific genetic therapies, functional readouts of CFTR activity resident within the lung are necessary to assess therapeutic and biological efficacy. Further enrollment of subjects to establish LAPD discrimination and normative values in CF disease state are underway."

Anesthesia • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Respiratory Diseases • CFTR

ENAC Blockade and Arterial Stiffness (clinicaltrials.gov) - P2/3 | N=157 | Active, not recruiting | Sponsor: University of Missouri-Columbia | Trial completion date: Feb 2025 ➔ Aug 2025

Trial completion date • Genetic Disorders • Obesity

Extracellular vesicles play a central role in linking podocyte injury to mesangial activation in glomerular disease. (PubMed, Theranostics) - "In vitro, Ang II-EVs induced the activation and proliferation of rat mesangial cells (HBZY-1), whereas inhibition of EV secretion with dimethyl amiloride, depletion of EVs from conditioned media or knockdown of Shh expression abolished the ability of Ang II-EVs to induce HBZY-1 activation... These findings suggest that podocyte injury can cause mesangial cell activation and glomerulosclerosis by releasing Shh-enriched EVs. Therefore, strategies targeting EVs may be a novel way to ameliorate proteinuric kidney disease."

Journal • Glomerulonephritis • Nephrology • Renal Disease • SHH

Repurposing High-Throughput Screening Reveals Unconventional Drugs with Antimicrobial and Antibiofilm Potential Against Methicillin-Resistant Staphylococcus aureus from a Cystic Fibrosis Patient. (PubMed, Antibiotics (Basel)) - "After performing a literature review to identify other, already published biological properties that could be relevant to the CF lung environment (i.e., activity against other CF pathogens, and anti-inflammatory and anti-virulence potential), the most interesting hits were the following: 5-(N,N-Hexamethylene)-amiloride (diuretic), Toremifene (anticancer), Zafirlukast (antiasthmatic), Fenretide (anticancer), and Montelukast (antiasthmatic) against planktonic S. aureus cells; Hemin against biofilm formation; and Heparin, Clemastine (antihistaminic), and Bromfenac (nonsteroidal anti-inflammatory) against established biofilms. These findings warrant further in vitro and in vivo studies to confirm the potential of repurposing these compounds for managing lung infections caused by S. aureus in CF patients."

Journal • Asthma • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases

Pregnancy, primary aldosteronism and renal tubular disorders: A systematic review of the utility of amiloride in pregnancy (ERA 2025) - No abstract available

Review • Endocrine Disorders

Novel Lung Cell Penetrating Peptides Target Airway Epithelial Type 2 Cells (ASGCT 2025) - "Endocytosis mechanisms were explored via FACS analysis of cyclic R11A (cR11A) uptake in HBECs treated with endocytosis inhibitors (Pitstop2, Amiloride, and Nystatin) and via confocal microscopy tracking co-localization with transferrin or the lysomal marker LAMP1...Notably, cR11A-siRNA conjugates targeting SARS-CoV-2 effectively inhibited viral replication in an air-liquid interface model of human lung cells, with EC₉₀ values of 0.64 ± 0.2 µM (cR11A-S1) and 1.04 ± 0.2 µM (cR11A-E2), compared to 0.019 µM for Remdesivir... We identified two novel LTPs, R11A and S7A, that targets ATII, basal cells and ionocytes after an intravenous delivery in as little as 15 min. Cyclization enhanced transduction efficiency in vitro and in vivo by enhancing serum stability. Uptake occurs via clathrin-mediated endocytosis, followed by endosomal escape."

Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • LAMP1 • TP63

What a MES!: A Case of Abiraterone-induced Mineralocorticoid Excess Syndrome (ENDO 2025) - "However, its dual inhibition of 17α-hydroxylase and 17,20-lyase can lead to adverse effects from cortisol suppression.A 79-year-old male with prostate carcinoma and bone metastases on Triptorelin pamoate every six months and abiraterone 250 mg twice daily with prednisone 5 mg once daily for over a year has hypertension with more than three anti-hypertensive medications, including a diuretic, and also has diabetes with chronic kidney disease...Abiraterone was discontinued, and prednisone was switched to dexamethasone due to its lack of mineralocorticoid activity. As amiloride was unavailable, finerenone, a selective mineralocorticoid receptor antagonist, was initiated.Abiraterone inhibits CYP17A1, reducing cortisol production by blocking 17α-hydroxylase and suppressing androgen synthesis, key for prostate cancer progression...Finerenone, a novel, selective MRA, is as effective as spironolactone with fewer side effects and better cardiovascular outcomes, particularly in..."

Clinical • Cardiovascular • Castration-Sensitive Prostate Cancer • Chronic Kidney Disease • Diabetes • Endocrine Disorders • Genito-urinary Cancer • Hypertension • Metabolic Disorders • Nephrology • Oncology • Prostate Cancer • Renal Disease • Solid Tumor • AR

A Case of Severe Polyuria: Diagnostic Challenges and Management of Nephrogenic Diabetes Insipidus (ENDO 2025) - "Treatment with hydrochlorothiazide (50 mg daily), amiloride (5 mg daily), and a low-salt, low-protein diet decreased urinary output to about 5 liters per day. Hereditary AVP-R, as seen in this patient, is a rare condition characterized by varying degrees of resistance to AVP. Approximately 90% of hereditary cases are linked to X-linked AVPR2 mutations (2,3), underscoring the importance of genetic testing. This case shows the difficulties in distinguishing AVP-R (NDI) from other causes of polyuria and demonstrates the pivotal role of desmopressin testing in confirming the diagnosis."

Clinical • Cardiovascular • Endocrine Disorders • Hypertension • Infectious Disease • Metabolic Disorders • Pneumonia • Respiratory Diseases

Nasal Potential Difference in Young Children is Feasible - Report from a National Referral Center. (PubMed, Respir Med) - "-NPD testing is feasable in very young children. This protocol could be valuable for investigating cases of CF screened positive indeterminate diagnosis (CFSPID) or CF metabolic syndrome (CFMS), and for pre- and post- testing in clinical trials. Further validation studies are warranted."

Journal • Anesthesia • Asthma • Immunology • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases

Lysergol exerts potent antiviral activity against the emerging Oropouche virus in vitro. (PubMed, Antiviral Res) - "We identified 13 hit compounds that were protective against OROV-induced cytopathic effect in cell culture, of which 3 were confirmed: lysergol, amiloride hydrochloride, and pyridostatin TFA, with EC50 values below 2 μM...In conclusion, our phenotypical screening campaign led to the identification of a first-in-class compound with potent antiviral activity against the emerging OROV in cell culture. We conclude that high-throughput screening assays can be implemented in response to the emergence of arboviruses and accelerate the discovery of candidate treatments."

Journal • Preclinical • Infectious Disease

Transgenically expressed human delta epithelial sodium channel facilitated fluid absorption in mouse fetal lung explants. (PubMed, Am J Physiol Lung Cell Mol Physiol) - "Amiloride treatments revealed that both α-ENaC and δ-ENaC contributed to fluid absorption...Further, specific blocking of α-ENaC using α-13 inhibitory peptide resulted in a 2.12-fold growth increase in WT explants, compared to a 1.47-fold increase in SCNN1D-Tg explants (p<0.001). In summary, this study provides evidence that δ-ENaC may contribute to fluid absorption in E15 and new-born lungs, highlighting its significance in alveolar fluid regulation in prenatal and postnatal lungs."

Journal • Preclinical

Endocytotic Albumin Uptake Pathways in Human Adipose Stem Cells and Connection to Intracellular Calcium Oscillations and the Neonatal Fc receptor (FcRn). (PubMed, Cells Tissues Organs) - "Our data demonstrated that endocytosis of albumin occurred by micropinocytosis (inhibition by cytochalasin D, wortmannin, and ethylisopropylamiloride (EIPA)), caveolae-dependent (inhibition by genistein and nystatin) and clathrin-mediated (inhibition by Dyngo-4a) pathways...Notably, not only intracellular albumin and IgG accumulation, but also Ca2+ oscillations were inhibited by the FcRn-blocking antibody nipocalimab which interferes with the IgG binding site of FcRn. Moreover, siRNA-mediated downregulation of FcRn protein expression significantly reduced intracellular albumin content, the number of cells displaying Ca2+ oscillations, and the duration and amplitude of Ca2+ signals. In summary, our data suggest that Ca2+ oscillations in human ASCs regulate albumin uptake and presumably IgG recycling via FcRn."

Journal

Invertebrate Bile Acid-Sensitive Ion Channels and Their Emergence in Bilateria. (PubMed, FASEB J) - "Using electrophysiological and pharmacological approaches, we show that invertebrate BASICs exhibit species-specific bile acid sensitivity profiles and differing responses to channel blockers, amiloride, and diminazene, while retaining shared properties like inhibition by calcium ions and selective permeability of sodium ions. For example, the acorn worm Schizocardium californicum BASIC displays broad bile acid sensitivity similar to mammals, while the brachiopod Novocrania anomala BASIC is activated solely by ursodeoxycholic acid (UDCA) in our experiments...Given the absence of endogenous bile acids in invertebrates, we propose that invertebrate BASICs may detect environmental compounds, contributing to ecological interactions. This study enhances our understanding of the evolutionary, functional, and ecological roles of BASICs, with implications for future research into their native ligands."

Journal • CNS Disorders • Psychiatry • Schizophrenia

A-CKD: Beneficial Effect of Amiloride on Progression of Chronic Kidney Disease (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Odense University Hospital

New P2 trial • Chronic Kidney Disease • Nephrology • Renal Disease

Electrocardiographic Left Ventricular Mass Trajectories and the Effects of Treatment in Patients at Different Stages of Hypertension. (PubMed, J Clin Med) - "In the PREVER-Treatment trial, those randomized to the chlorthalidone/amiloride combination or losartan experienced a similar reduction in electrocardiographic LVM during the 18 months of treatment (p < 0.01). The institution of low-dose antihypertensive drug therapy in prehypertension and treatment of patients with stage 1 hypertension has the potential to interrupt the progress of hypertensive cardiomyopathy."

Journal • Cardiomyopathy • Cardiovascular • Hypertension