amiloride hydrochloride / Generic mfg. - LARVOL DELTA

Mechanistic insights into opioid-induced pulmonary edema: receptor specificity and sodium transport. (PubMed, Ir J Med Sci) - "Opioid-induced AFC impairment involves receptor-specific alterations in alveolar fluid regulation, with the DOR playing a dominant inhibitory role, suggesting its involvement in the development of pulmonary edema."

Journal • Acute Respiratory Distress Syndrome • Addiction (Opioid and Alcohol) • Anesthesia • Cardiovascular • Pain • Respiratory Diseases

PRL-3 enhances multiple myeloma cell survival in acidic microenvironments via metabolic adaptation and pH regulation. (ASH 2025) - "Pharmacologic inhibition of lactate and proton transport was performed using Syrosingopine (dualMCT inhibitor), AZD0095 (MCT4 inhibitor), AZD3965 (MCT1 inhibitor), Bafilomycin A1 (v-ATPase inhibitor),and ethyl isopropyl amiloride (EIPA; NHE1 inhibitor). Thissuggests compensatory roles among transporters and pathways whose importance varies depending onthe pH level. Increased metabolism and proton transport are associated with high PRL-3 expression,supporting PRL-3 as a key protein for cell survival in acidic conditions and a potential therapeutic targetin myeloma treatment."

Hematological Malignancies • Multiple Myeloma • ANXA5 • PTP4A3 • SLC16A1

Severe lithium-induced nephrogenic diabetes insipidus: The diuresis paradox. (PubMed, S Afr Med J) - "Amiloride with hydrochlorothiazide adequately reduced the polyuria. Management of lithium-induced NDI remains complex, and includes diuretics, which paradoxically reduce polyuria in this setting. Failure to follow up critical results led to profound morbidity, and is a crucial learning point in this case."

Journal • Bipolar Disorder • CNS Disorders • Critical care • Metabolic Disorders • Mood Disorders • Psychiatry • Renal Disease

Molecular Dynamics Insights into TAS1R2 Transmembrane Domain Activation. (PubMed, Int J Mol Sci) - "Previous studies demonstrated that the sweetener S819 and the sweet inhibitor amiloride act through the transmembrane domain (TMD) of TAS1R2; however, the molecular mechanisms underlying these ligand-specific effects remain unclear, largely due to the historical lack of experimentally determined full-length STR structures...Additional analyses uncovered ligand-specific rearrangements in hydrogen-bonding and hydrophobic interaction networks. These results provide atomistic insights into how agonists and antagonists differentially modulate TAS1R2 activation and lay a structural foundation for designing novel sweeteners and taste modulators."

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Amiloride: revisiting an old drug for resistant hypertension. (PubMed, Clin Hypertens) - "The findings from the SPARE trial suggest that amiloride may be a viable alternative to spironolactone for RH, particularly in patients who are intolerant to mineralocorticoid receptor antagonists. While spironolactone remains the preferred option due to its established role in blocking systemic aldosterone activation and proven cardiovascular benefits, amiloride can provide a practical and well-tolerated alternative."

Journal • Review • Cardiovascular • Fibrosis • Hypertension • Immunology • Women's Health

Polystyrene nanoplastics promote fish iridovirus replication via inducing inflammatory response, antioxidant damage and enhancing viral entry. (PubMed, Environ Pollut) - "In contrast, methyl-β-cyclodextrin and ethyl-isopropyl amiloride treatment exhibited no regulatory effects, suggesting that PS-NPs internalization and promoted SPIV replication via the clathrin-mediated endocytosis in vitro. Overall, our findings offer new insights into the pro-viral actions of PS-NPs on fish iridovirus infection in vitro, which highlights a potential threat of NPs to aquatic viral diseases."

Journal • Infectious Disease • Inflammation

APAM: Acid-Sensing Ion Channel and Migraine Disease Proof of Concept Study on the Efficacy of Amiloride in the Prophylaxis of Migraine Aura (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Centre Hospitalier Universitaire de Nice | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • CNS Disorders • Migraine • Pain

Ovarian Hormones Moderate Systolic Hypertension in Female Eln Haploinsufficient Mice. (PubMed, bioRxiv) - "Furthermore, amiloride lowered SBP and increased urinary Na + excretion, suggesting that Eln +/- -induced hypertension may be Na + -dependent. We conclude that increased Na + and water retention by the kidney contribute to hypertension resulting from Eln haploinsufficiency. The underlying mechanism involves the alteration of ovarian hormone effects in the kidney and sustained signaling downstream of the V 2 receptor, leading to increased ENaC activity and water reabsorption."

Journal • Preclinical • Cardiovascular • Developmental Disorders • Genetic Disorders • Hypertension

Copper uptake in blue crabs is independent of sodium transport under hyposaline conditions. (PubMed, Comp Biochem Physiol C Toxicol Pharmacol) - "Specific inhibitors targeting Na+/H+ exchangers (amiloride, 100 μM) and Na+, K+, 2 Cl- cotransporters (NKCC) (furosemide, 120 μM) were used. The 64Cu accumulated mainly in the carapace (49 %) and posterior gills (22 %), regardless of Na+ availability. The findings clearly demonstrate that Cu uptake, irrespective of the uptake pathway, proceeds independently of Na."

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Na+/H+ Exchanger 1 Inhibition Overcomes Venetoclax Resistance in Acute Myeloid Leukemia. (PubMed, Cells) - "Our results demonstrated that co-treatment with venetoclax and the NHE1 inhibitor 5-(N,N-hexamethylene) amiloride (HMA) synergistically induced apoptosis in both venetoclax-sensitive and -resistant leukemic cell lines. Furthermore, co-treatment downregulated the anti-apoptotic protein MCL-1 and reduced PI3K and Akt phosphorylation, suggesting that inhibition of these survival pathways also contributed to the synergistic effect. Inhibition of NHE1 may substantially enhance venetoclax sensitivity in certain AML models, particularly in venetoclax-resistant THP-1 cells but not in U-937, highlighting biological diversity and the probable involvement of alternative survival pathways."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BAX • CASP3 • CASP9 • MCL1

Piezo1 Mediates Deoxycorticosterone Acetate-Salt Hypertension Through Renal Epithelial Sodium Channel Activation in the Kidneys (KIDNEY WEEK 2025) - "Yoda1 markedly induced increased Na + influx in mpkCCD cells, which was significantly blocked by amiloride. ICG001 significantly attenuated the mechanical force or Yoda1-induced upregulation of β-catenin and ENaC subunits. Conclusion Piezo1 activation induced increased blood pressure likely through upregulating ENaC expression in the kidney of mice with DOCA-salt by activating β-catenin pathway."

Cardiovascular • Hypertension • Nephrology • Renal Disease

Amiloride Is Noninferior to Spironolactone for Resistant Hypertension. (PubMed, Am Fam Physician) - No abstract available

Journal • Cardiovascular • Hypertension

ATP increases murine neuroblastoma cell size through a PANX1- and macropinocytosis-dependent mechanism. (PubMed, Biol Open) - "Amiloride treatment and mutation of an extracellular tryptophan (W74) in PANX1 abolished ATP-evoked cell area enlargement, suggesting that PANX1 may itself regulate this form of macropinocytosis...Several lipid-PANX1 interactions were identified with relevance to macropinocytic mechanisms. The role of PANX1 in ATP-mediated macropinocytosis could be particularly important for disease states implicating PANX1, such as cancer, where ATP can act as a purinergic regulator of cell growth/metastasis and as a supplementary energy source following internalization."

Journal • Preclinical • Neuroblastoma • Oncology • Solid Tumor

Lysosomal Membrane Permeabilization Sensitizes Ctss-Hyperactive Tumors to BCL2-Targeting Therapies (ASH 2023) - "We next employed LMP-inducing tool compounds (LLOMe) and clinically used drugs or analogs (desipramine, hexamethylene amiloride) to release cathepsins into the cytosol...The combination of LLOMe-induced LMP and the BCL2 inhibitor venetoclax (VEN) showed increased cytotoxicity in CTSS-hyperactive Karpas422 cells compared to monotherapy and CSTB k/d enhanced this phenotype (Fig A, bottom)...In summary, we show that CSTB is a functionally relevant inhibitor that determines the net activity of LMP-released cytosolic CTSS. Furthermore, LMP-inducing therapies may be a promising approach to sensitize CTSS-hyperactive tumors towards apoptosis by proteolytic cleavage of BCL2 family members."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • BCL2 • BCL2L1 • CTSS • MCL1

Drug-associated hypertensive crisis: a disproportionality analysis of the FAERS database. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Ramipril (282 cases) and valsartan (192 cases) ranked as the second and third medications, respectively. The top 5 drugs associated with the risk of hypertensive crisis under the ROR algorithm were amlodipine perindopril (ROR = 136.64), methyl aminolevulinate (ROR = 122.78), tranylcypromine (ROR = 105.15), rifapentine (ROR = 39.46), and amiloride hydrochlorothiazide (ROR = 39.36)...Our study showed that numerous medications carry potential risks for drug-associated hypertensive crisis. Further investigation is required to establish causality and inform clinical decision-making."

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Divergent Effects of Calcium Channel Modulators on H-Reflex Excitability in Fatigued Rat Muscle. (PubMed, Int J Mol Sci) - "Using the Hoffmann reflex (H-reflex) as an indicator of motoneuron excitability, we evaluated the effects of Ca2+ channel blockers (Amiloride, Nifedipine) and an activator ((-)-Bay K8644) on the reflex responses of the plantar muscle before and after fatigue induction. These findings demonstrate that pharmacological modulation of Ca2+ channels has distinct and divergent effects on spinal excitability during fatigue. These results highlight the close interaction between intramuscular Ca2+ regulation and reflex pathways and suggest potential strategies for enhancing muscle performance through targeted Ca2+ channel modulation."

Journal • Preclinical • Fatigue

New Mutations in Bartter Syndrome (BS) Type 1 (KIDNEY WEEK 2025) - "Case Description We describe a 22-year-old male with a history of severe hypokalemia managed with potassium supplements and amiloride who presented after routine labs revealed severe hypokalemia following missed doses of both medications...Prior genetic analyses were limited to sequential single-gene testing, an approach that was time-consuming, costly, and lacked complete diagnostic yield. This case illustrates the value of re-evaluating genetic testing in patients with previous inconclusive results to help identify novel mutations, as advances in technology now allow for the detection of mutations previously undetectable."

Metabolic Disorders • Nephrology • Rare Diseases

Renal Tubular Dysfunction as the Driving Force Behind Refractory Hypokalemia in Ogilvie Syndrome (KIDNEY WEEK 2025) - "This report details the case of a 57-year-old male with IgG kappa multiple myeloma undergoing treatment with daratumumab, lenalidomide, and dexamethasone (DRd) who developed severe Ogilvie's syndrome complicated by refractory hypokalemia (K ≤3.1 mEq/L despite aggressive IV repletion). The 48-hour lag between potassium normalization (Day 3) and colonic recovery (Day 5) demonstrates that electrolyte correction must precede functional GI improvement. Amiloride's effectiveness supports ENaC blockade as superior to mineralocorticoid antagonism in chemotherapy-induced tubular disorders."

Addiction (Opioid and Alcohol) • Endocrine Disorders • Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • Nephrology • B2M

Persistent Hypokalemia: A Manifestation of Long COVID Syndrome? (KIDNEY WEEK 2025) - "Initial oral potassium/Amiloride therapy improved potassium but caused intolerance, leading to weekly intravenous potassium chloride infusions, maintaining serum potassium around 3 mmol/L...Clinicians should consider Long COVID in new-onset persistent hypokalemia. Further research into prevalence and mechanisms is warranted."

Infectious Disease • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases

Ogilvie Syndrome and Abiraterone: Untangling Two Uncommon Causes of Refractory Hypokalemia (KIDNEY WEEK 2025) - "He was started on medication regimen of Amiloride, Eplerenone, and prednisone. This results in increased sensitivity to normal serum aldosterone levels and persistent, predominantly colonic, potassium wasting. This explains this patient’s improvement on aldosterone antagonists, as it worked to suppress expression of BK channels, as well as treatment of pseudo-obstruction."

Endocrine Disorders • Genito-urinary Cancer • Hypertension • Infectious Disease • Nephrology • Prostate Cancer • Renal Disease • Septic Shock • Solid Tumor

Liddle Syndrome: Clinical Phenotype and Therapeutic Response in a Novel Heterozygous SCNN1G Variant (KIDNEY WEEK 2025) - "Despite multiple antihypertensive medications (including spironolactone), over the years her blood pressure had remained elevated (range: 145/80-155/85 mmHg)...Treatment was modified to include amiloride (ENaC blocker), with discontinuation of potassium supplements...The patient was referred for genetic counseling for family planning afterward. Discussion This case highlights several important teaching points: (1) Liddle syndrome should be considered in patients with treatment-resistant hypertension and hypokalemia across all age groups; (2) SCNN1G variants, though less common, can present with classical Liddle syndrome features; (3) Clinical response to ENaC blockers may provide diagnostic confirmation when genetic findings are inconclusive; (4) Family screening is essential due to the autosomal dominant inheritance pattern; (5) Ongoing identification and functional characterization of novel ENaC variants is crucial, as expanding the spectrum of pathogenic variants..."

Clinical • Cardiovascular • Hypertension • Nephrology

A Case of Abiraterone-Induced Mineralocorticoid Excess Syndrome Associated with Rhabdomyolysis and Polyuria (KIDNEY WEEK 2025) - "After resuming prednisone and starting amiloride, his hyperkalemia resolved first, followed by gradual resolution of rhabdomyolysis and polyuria. Second, there has been historical reports of hypokalemia-associated tubular concentrating defects through disruption of AQP2 production. Despite treatment, both rhabdomyolysis and polyuria continued until successful normalization of serum potassium suggesting that the hypokalemia was the primary driver of our patient's presentation."

Clinical • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Hypertension • Prostate Cancer • Renal Disease • Solid Tumor

mTORc2 Stimulates Renal Potassium (K+) Excretion During Overnight-High-K+ by Simultaneously Stimulating Epithelial Sodium Channel (ENaC)/Potassium Kir1.1 Channel (ROMK) and Inhibiting Kir4.1/Kir5.1 (KIDNEY WEEK 2025) - "Funding NIDDK Support Background The mTORc2 is a multiprotein complex and RICTOR (rapamycin insensitive companion of mTOR) is one of the core components of mTORc2...In contrast, amiloride-sensitive Na + -currents (ENaC) and tertiapin-Q (TPNQ)-sensitive-K + -currents (ROMK) were lower in both late-DCT/early-connecting-tubule (CNT) and cortical- collecting-duct (CCD) of Ks-RICTOR-KO mice than Rictor flox/flox mice...It mediates the effect of high-K + -intake on ENaC and ROMK not only in the CCD but also in late-DCT/early-CNT. The mTORc2 plays a key role in stimulating renal K + excretion during high-K + -loading by simultaneously inhibiting Kir4.1/Kir5.1 and stimulating ENaC and ROMK."

RICTOR

Gain- and Loss-of-Function Variants in Epithelial Sodium (Na+) Channel Delta Subunit (KIDNEY WEEK 2025) - "Amiloride-sensitive currents (0.1 mM) representing ENaC activity were measured and compared within the same baches of oocytes expressing the WT or mutant channels...Conclusion Our results suggest that R297C is a gain-of-function low-frequency variant and G71S and C370R are loss-of-function rare variants of δENaC. These and other δENaC variants may contribute to the reported association between δENaC and blood pressure."

Empagliflozin Counters Metolazone-Induced Hypomagnesemia and Modifies Renal Ion Transporters and Channels (KIDNEY WEEK 2025) - "Hydrochlorothiazide response test showed EMPA did not reverse MET-induced NCC inhibition, while furosemide response test showed NKCC2 activity did not differ among the treatment groups. However, amiloride response test suggests EMPA may further inhibit ENaC-dependent K + secretion. Abundance of pAQP2 was significantly lower in MET and higher in EMPA mice. Conclusion EMPA could correct drug-induced hypomagnesemia, though it exerts complex effects on renal ion channels and transporters in response to polyuria."

Metabolic Disorders • CALB1