amiloride hydrochloride / Generic mfg. - LARVOL DELTA

Macropinocytosis inhibition attenuates pro-fibrotic responses in lung fibroblasts and pulmonary fibrosis. (PubMed, bioRxiv) - "The inhibition of macropinocytosis with 5-(n-ethyl-n-isopropyl)-amiloride (EIPA) significantly inhibited profibrotic responses in IPF-derived and TGF-β1-stimulated HLFs...Both genetic and pharmacological inhibition of macropinocytosis significantly ameliorated pulmonary fibrosis in bleomycin (Bleo)-injured mice...Finally, we found that imipramine (Imi), a tricyclic antidepressant approved by the Food and Drug Administration (FDA), effectively inhibited macropinocytosis and ameliorated profibrotic responses in lung fibroblasts, Bleo-injured mice and IPF-derived PCLS. Taken together, our results suggest macropinocytosis inhibition as a potential therapeutic strategy to treat pulmonary fibrosis."

Journal • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • MEOX1 • TGFB1

The Clinical Spectrum of Acquired Hypomagnesemia: From Etiology to Therapeutic Approaches. (PubMed, Biomedicines) - "Management strategies include magnesium supplementation and adjunctive therapies like amiloride and SGLT2 inhibitors to reduce renal magnesium losses. Recognizing and addressing drug-induced hypomagnesemia is essential to improve patient outcomes and prevent long-term complications."

Journal • Review • Cardiovascular • Oncology

Canagliflozin inhibits electrogenic Na+ transport in mouse cortical collecting duct cells. (PubMed, Function (Oxf)) - "Canagliflozin inhibited ENaC-dependent Na+ transport (amiloride-sensitive short circuit current; ISC) in mCCDcl1 cells while empagliflozin had no effect. We identify Na+ transport through ENaC and the Na+/K+ ATPase as novel targets of inhibition by canagliflozin, with Sgk1 as a likely upstream mechanistic component. Canagliflozin-specific effects on transport mediated via this mechanism may contribute to non-class effects of this drug observed clinically."

Journal • Preclinical

Inhibition of senescence-associated β-Galactosidase by Amiloride in senescent airway epithelial cells (ERS 2025) - No abstract available

Pulmonary Disease • Respiratory Diseases

AntimiR uptake by human proximal tubule epithelial cells is predominantly by macropinocytosis. (PubMed, Sci Rep) - "Megalin inhibition with receptor associated protein to target receptor-mediated endocytosis had no effect on antimiR uptake, whereas the macropinocytosis inhibitor 5-(N-ethyl-N-isopropyl)-amiloride reduced antimiR uptake. Our results demonstrate antimiR can be delivered to primary human PTEC in vitro without the use of transfection reagents and support macropinocytosis as the dominant pathway of antimiR entry."

Journal • Nephrology • Reperfusion Injury • Transplantation

Extracellular serine proteases activate amiloride-insensitive ENaC channels and decrease migration and invasion ability of human leukemia cell lines. (PubMed, Am J Physiol Cell Physiol) - "Epithelial sodium channels (ENaCs) have been reported to affect cancer cell development, including the processes of proliferation, apoptosis, and cell motility. Moreover, there was no effect of α-chymotrypsin on the migration of MOLT-4 leukemia cells, which do not express functionally active ENaCs. Our data imply that extracellular serine proteases, as universal regulators of sodium permeability via ENaC, decrease leukemia cells migration."

Journal • Preclinical • Hematological Malignancies • Leukemia • Oncology

Phospholipase A2 from Daboia siamensis venom induces acute kidney injury: involvement of ion channels in an isolated perfused rabbit kidney model. (PubMed, J Venom Anim Toxins Incl Trop Dis) - "Twenty IPKs were allocated into five groups (n = 4 each): (1) RvPLA₂ in calcium-deficient modified Krebs-Henseleit solution (MKHS), (2) RvPLA₂ in standard MKHS, (3) RvPLA₂ following pretreatment with verapamil (a voltage-gated Ca²⁺ channel blocker), (4) RvPLA₂ following pretreatment with amiloride (a Na⁺ channel blocker), and (5) RvPLA₂ following pretreatment with minoxidil (a KATP channel opener). The RvPLA2 activity requires Ca2+ for activation which may target distinct sites on the cell membrane, including ion channel receptors in nephrons. The effects of RvPLA2 on glomerular and renal tubular function are independent and cannot be modified by pretreatment with different ion channel blockers."

Journal • Preclinical • Acute Kidney Injury • Nephrology • Renal Disease

LncRNA AFAP1-AS1 promoting residual tumor progression after insufficient radiofrequency ablation by up-regulating macropinocytosis in hepatocellular carcinoma. (PubMed, Cell Signal) - "Our findings revealed AFAP1-AS1's oncogenic role and proposed its potential as a diagnostic marker and therapeutic candidate for residual tumor progression and macropinocytosis suppression in HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • AFAP1-AS1 • EGFR • MIR139

Novel Lung Cell-Penetrating Peptide Targets Alveolar Epithelial Type II Cells, Basal Cells, and Ionocytes. (PubMed, Pharmaceutics) - "Endocytosis studies showed a decrease in peptide uptake by pre-treatment with Pitstop2 but not Amiloride or Nystatin. The uptake mechanism appears to be via clathrin-mediated endocytosis with escape from endocytic vesicles. cR11A can act as a vector to deliver anti-viral siRNA to epithelial cells."

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

Diagnosing apparent mineralocorticoid excess in a child with hypertension and nephrocalcinosis: from symptoms to genetics. (PubMed, CEN Case Rep) - "The treatment with amiloride and spironolactone resulted in normalized urine output, stabilized blood pressure, and balanced electrolyte levels. This case emphasizes the importance of considering AME in pediatric patients presenting with unexplained refractory hypertension associated with hypokalemia and nephrocalcinosis, and it underscores the crucial role of genetic testing in diagnosis and management."

Journal • Cardiovascular • Genetic Disorders • Hypertension • Metabolic Disorders • Nephrology • Pediatrics

A mechanistic investigation of the effects of lactic acidosis on myocardial contractility in the Neotropical fast-swimming freshwater fish Brycon amazonicus. (PubMed, Comp Biochem Physiol C Toxicol Pharmacol) - "Isometric ventricular preparations were utilized to assess: (a) the effects of LA; (b) the combined effects of LA and ryanodine, an inhibitor of sarcoplasmic reticulum (SR) function; (c) the combined effects of LA and amiloride, an inhibitor of the Na+/H+ exchanger (NHE); (d) the effects of lithium, an inhibitor of the Na+/Ca2+ exchanger (NCX), and its interaction with LA; and (e) the effects of a Ca2+-free solution and its interaction with LA...This strategy involves coordinated sarcoplasmic reticulum (SR) Ca2+ release and activation of the NHE to restore myocardial performance. Such physiological adjustments likely support survival during intense anaerobic activity in fluctuating aquatic environments."

Journal • Metabolic Disorders

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 • Chronic Kidney Disease • Diabetes • Endocrine Disorders • Genito-urinary Cancer • Hormone Sensitive Prostate 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) - "Background:Arginine vasopressin V2 resistance (AVP-R), commonly known as nephrogenic diabetes insipidus (NDI), is an uncommon disorder in which the kidneys fail to respond to AVP, causing significant polyuria. 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

The potentiating activity of benzodiazepine site of the GABA(A) receptor is inhibited by competitive antagonists of orthosteric site. (PubMed, Neurochem Int) - "In this work, we studied the influence of competitive antagonists of the GABAA receptor gabazine (GBZ), bicuculline (Bic), and amiloride (Ami) on the potentiating effect of the agonist of BDZ site zolpidem (Zolp)...The results show that the potentiating effect of Zolp is reduced by half in the presence of competitive GABAA receptor antagonists (p < 0. 001)."

Journal

From mechanism to therapy: How EIPA modulates dendritic cell-mediated allergic responses via IL-12b and TIM4. (PubMed, Biomed Pharmacother) - "Ethylisopropylamiloride (EIPA) has been shown to attenuate immune inflammation...Consequently, the Th2 response and airway allergy were mitigated. In conclusion, EIPA attenuates the allergic response by upregulating IL-12b production, reducing TIM4 expression in DCs, and suppressing the Th2 response."

Journal • Allergy • Immunology • Inflammation • Targeted Protein Degradation • IL12B • KDM4D

Loss of cadherin 17 downregulates LGR5 expression, stem cell properties and drug resistance in metastatic colorectal cancer cells. (PubMed, Cell Death Dis) - "Consequently, the loss of CDH17 increased sensitivity to 5-FU, irinotecan, oxidative stress and anoikis in CRC cells...In conclusion, CDH17 plays a crucial role in maintaining colorectal cancer cell stemness and chemoresistance via LGR5/Wnt/MYC signaling and SLC38A5 expression. These findings underscore the therapeutic potential of CDH17 targeting in metastatic CRC, and support the use of amiloride for inhibiting liver metastasis."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CDH17 • DSC1 • LGR5 • SLC38A5

Dual Diagnostic Dilemma: Gitelman Syndrome and Incidental Neuroendocrine Tumor in a Young Adult With Refractory Hypokalemia. (PubMed, Cureus) - "Management comprised high-dose potassium and magnesium supplementation, amiloride, octreotide, and everolimus. Moreover, it emphasizes the limitations in managing double disease entities in a young individual and the insurmountable hurdles for advanced treatments like peptide receptor radionuclide therapy in underdeveloped nations. This report highlights the importance of further studying the association between the interplay of genetic syndromes (such as Gitelman syndrome) and associated neoplasms, as well as the vital coordination of complex and multidisciplinary management in rare clinical situations."

Journal • Cardiovascular • Diabetes • Embryonal Tumor • Endocrine Cancer • Hepatocellular Cancer • Hypertension • Metabolic Disorders • Nephrology • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • Type 1 Diabetes Mellitus • SSTR

Severe Late-Onset Abiraterone-Induced Hypokalemia in a Diabetic Patient With Concomitant Adrenal Gland Incidentaloma: A Diagnostic Challenge. (PubMed, Case Rep Endocrinol) - "Physicians should consider dexamethasone over prednisone in persistent MES cases, always monitoring also for the risk of developing Cushing syndrome. Given the rising prostate cancer incidence, clinicians must remain vigilant for MES-related complications with abiraterone, including delayed-onset severe hypokalemia."

Journal • Cardiovascular • Castration-Resistant Prostate Cancer • Cushing’s Disease • Diabetes • Endocrine Disorders • Genito-urinary Cancer • Hypertension • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor

Embryo-derived trypsin-induced calcium entry is inhibited by endometrial infertility factor, LEFTY2. (PubMed, Front Cell Dev Biol) - "Treatment of endometrial cells with trypsin was followed by an increase of [Ca2+]i, an effect that was significantly blunted by amiloride and LEFTY2. Taken together, we demonstrate that high trypsin levels are associated with a positive pregnancy outcome and that infertility factor LEFTY2 downregulates trypsin induced Ca2+ increase due in part by interference with nifedipine sensitive Ca2+ entry. These findings contribute further to our knowledge of unexplained infertility and failed assisted reproductive technologies."

Journal • Infertility • Sexual Disorders

CARD: Safety and Efficacy of Chlorthalidone + Amiloride to Elderly Patients Treatment With Arterial Hypertension (clinicaltrials.gov) - P3 | N=246 | Completed | Sponsor: Eurofarma Laboratorios S.A. | Unknown status ➔ Completed

Trial completion • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension

Ifosfamide-Induced Partial Arginine Vasopressin Resistance Responsive to Vasopressin/Desmopressin and Amiloride. (PubMed, Cureus) - "This is a case of partial arginine vasopressin resistance following the sixth cycle of doxorubicin-ifosfamide-mesna therapy for recurrent spindle cell sarcoma of the thigh. The diagnosis was confirmed with serum and urine chemistry testing showing urine hypo-osmolality (161 mOsm/kg) with polyuria (4.8 L urine output) in 24 hours, serum hyperosmolality (355 mOsm/kg), and an elevated baseline plasma copeptin of 82 pmol/L. Treatment with intravenous vasopressin followed by amiloride and supraphysiologic doses of oral desmopressin improved symptomatic hypernatremia."

Journal • Metabolic Disorders • Oncology • Sarcoma • Solid Tumor • Spindle Cell Sarcoma

Pregnancy, primary aldosteronism and renal tubular disorders: A systematic review of the utility of amiloride in pregnancy (ERA 2025) - "Pregnancy often presents the first opportunity to diagnose serious disease in women. Hypertension is frequently attributed as being pathognomonic of preeclampsia when associated with intrauterine growth retardation, leading to a failure to consider secondary testing. While there may be a negative reporting bias for side effects of amiloride during pregnancy, it has been used successfully and appears to be low risk base on the reported cases."

Review • Cardiovascular • Endocrine Disorders • Glomerulonephritis • Gynecology • Hypertension • Nephrology • Renal Disease

Blood pressure modulation through altered Epithelial Sodium Channel (ENaC) expression induced by microbiome exchange between Milan normotensive and hypertensive rat strains (ERA 2025) - "Putative role of ENaC on enhanced SBP in MN-HOM was further suggested by amiloride challenging on these rats, in which MN-HOM showed a reduction in SBP comparable to MN-BSL after amiloride treatment. We have demonstrated that the hypertensive phenotype in NA rats was transferred to MN rats through homogenization, indicating that the intestinal microbiota or metabolites derived therefrom could modulate ENaC in the cortex and eventually modulate SBP. Further studies are underway to identify metabolites from gut microbiota which may modulate ENaC and eventually blood pressure."

Preclinical • Cardiovascular • Hypertension

Amiloride synergizes with EGFR PROTACs and inhibitors to overcome therapeutic resistance in NSCLC. (PubMed, Bioorg Chem) - "Among NSCLC patients, approximately 15-30 % harbor activating mutations in the Epidermal Growth Factor Receptor (EGFR), making them eligible for treatment with tyrosine kinase inhibitors (TKIs) like osimertinib, which has shown significant therapeutic benefits. Collectively, MK-870 synergizes with EGFR-targeting agents through coordinated modulation of sodium channel proteins and NHE-mediated pH homeostasis. These novel insights highlight MK-870 as a promising adjuvant for overcoming EGFR-targeted therapeutic resistance in NSCLC, offering a new avenue for improving patient outcomes in this challenging disease."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • EGFR

Optimizing Anesthesia for High-Risk Patients: Scalp Block for Frontal Lobe Epithelioma Excision (Euroanaesthesia 2025) - "His medications included furosemide, pantoprazole, prednisone, hydroxychloroquine, apixaban, and amiloride...A landmark – guided scalp block targeting the supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, lesser and greater occipital nerves bilaterally was performed using 1 mL of 0.5% ropivacaine and 1 mL of 1% lidocaine at each injection point...Scalp block is an effective anesthesia and analgesia strategy for head surgery. RA enhances quality of recovery."

Clinical • Anesthesia • Atrial Fibrillation • Benign Prostatic Hyperplasia • Cardiovascular • Cognitive Disorders • Hepatology • Musculoskeletal Pain • Pain • Pulmonary Arterial Hypertension