acetazolamide / Generic mfg. - LARVOL DELTA

Balancing the "Faucet" and the "Drain": A Dual-Target Pharmacological Perspective on Fluid Dynamics in High-Altitude Cerebral Edema. (PubMed, Curr Vasc Pharmacol) - "From this perspective, a potential pharmacological paradox emerges: acetazolamide, a first-line preventive drug, has been proposed to act as a non-specific inhibitor of AQP4 and could, in theory, attenuate the clearance function of the glymphatic system, although direct clinical evidence for this effect remains limited. We propose a "dual-target" pharmacological strategy that seals the microvascular endothelium and enhances the clearance of glymphatic fluid. Combined with emerging vascular-targeted drugs, nanomedicines, and non-invasive delivery methods, this approach may offer a complementary framework for the prevention and treatment of severe high-altitude-related neurological diseases."

Journal • CNS Disorders

Design, synthesis and network pharmacology-integrated evaluation of benzenesulfonamides as potential Dickkopf-1 (Dkk-1)-targeting anticancer candidates. (PubMed, RSC Adv) - "Out of all the synthesized derivatives, compound 4d exhibited significant inhibitory potential against CA-II, with an IC50 value of 0.348 ± 0.024 µM, which is about 3-fold higher than that of the reference drug acetazolamide (IC50 = 0.9979 ± 0.0024 µM)...Finally, the present work has the potential to pave way for new therapeutic approaches in cancer treatment with the involvement of the less explored Dkk1 signaling target. In addition, a network pharmacology analysis of compound 4d against pancreatic cancer identified 243 shared targets that converged, through protein-protein interactions and enrichment analyses, on the PI3K-AKT and receptor tyrosine kinase signalling axes, providing a system-level rationale for its anticancer potential."

Journal • Oncology • Pancreatic Cancer • Solid Tumor • DKK1 • ELANE

What is the optimal PET scan time for quantification of brain perfusion from 15 O[H2O] PET? (EANM 2026) - "Materials and Our protocol includes two 6-minute PET/CT scans, separated by an injection of a vasodilator (acetazolamide)... Our results show that analysis with the Zhou model of a three-minute acquisition, shows high correlation with the six minutes acquisition, and lower symmetric mean relative difference, when voxel based analysis is needed. Therefore, it may be preferable when a reduced protocol duration is needed for example to reduce arterial blood sampling volume. Reducing scanning time, patient comfort increases and imaging becomes more effective."

Acetazolamide-Challenge Cerebral Perfusion SPECT-CT in the Management of Moyamoya Disease. (EANM 2026) - "Acetazolamide challenge SPECT-CT successfully identified exhausted cerebrovascular reserve, guiding surgical decision-making. Direct STA-MCA bypass restored cerebral perfusion with objective improvement on postoperative imaging and complete clinical resolution, supporting the role of acetazolamide challenge SPECT-CT for both preoperative risk stratification and postoperative efficacy assessment in moyamoya disease."

Cardiovascular • CNS Disorders • Vascular Neurology

Precision Pharmacotherapy for Obstructive Sleep Apnea: Matching Targeted Drugs to Patient Endophenotypes. (PubMed, Pharmaceuticals (Basel)) - "Carbonic anhydrase inhibition with acetazolamide or sultiame and selected sedating agents address ventilatory instability and a low arousal threshold, while solriamfetol and pitolisant relieve residual sleepiness. Mechanism-informed pharmacotherapy for OSA is now clinically credible, but scalable bedside endotyping, attention to tolerability, and trait-stratified trials are needed before treatment can be called endotype-guided."

Journal • Review • Genetic Disorders • Obesity • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Neurovascular changes in DOCA-hypertension model in mice (Neuroscience 2026) - "A decreased response to Acetazolamide, a carbonic anhydrase inhibitor and a potent vasodilator, was detected with fUS imaging, indicating impaired vascular reactivity in DOCA mice. Decrease was significant in cortex and present as trend in hippocampus and thalamus. DOCA mice also showed decreased response to Whisker stimulation compared to Sham mice indicating functional hyperemia"

Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • FUS

Clinical Profile and Visual Outcomes of Pre- and Postembolization of Carotid-cavernous Fistula-induced Glaucoma. (PubMed, Ann Afr Med) - "Medical management included topical dorzolamide, beta-blockers, and oral acetazolamide for IOP control. Visual acuity improved from counting fingers to 6/12 with successful preservation of optic nerve function. This case highlights the importance of timely multispecialty collaboration between ophthalmology and interventional radiology in managing CCF-related secondary glaucoma."

Journal • Cardiovascular • Glaucoma • Ophthalmology

Beyond the classic ketogenic diet: A systematic review of alternative and adjunctive therapies for GLUT1 deficiency syndrome. (PubMed, Epilepsy Res) - "While CKD remains the reference standard for GLUT1-DS management, selected alternative and adjunctive therapies may offer clinically meaningful benefit in specific clinical contexts. The current evidence base, however, is limited. These findings support cautious and individualized use of alternative therapeutic strategies while highlighting the need for larger prospective studies and standardized outcome measures to better define their role in GLUT1-DS management."

Journal • Review • CNS Disorders • Epilepsy • Metabolic Disorders • Movement Disorders • Pediatrics • SLC2A1

Erythroid anion exchanger-1 (SLC4A1) modulates carbonic anhydrase inhibitor acetazolamide on respiration. (PubMed, Front Physiol) - "This supports that AE1 and CAII function in concert to facilitate intraerythrocytic CO2/HCO3 - conversion for CO2 expiration. Since murine RBC-AE1 could help sensitize respiratory responses to acetazolamide-induced systemic CA inhibition, it warrants future clinical investigation to identify the appropriate dosing of acetazolamide for people with the GP.Mur blood type."

Journal • Metabolic Disorders • SLC4A1

Steric Control of Competitive Versus Noncompetitive Lactoperoxidase Inhibition by Amide-Linked Iridium(III) Complexes. (PubMed, Arch Pharm (Weinheim)) - "Kinetic analysis using LPO purified from bovine milk revealed nanomolar inhibition (IC50 = 0.64-3.12 nM; Kᵢ = 0.05 ± 0.01-5.36 ± 1.88 nM), representing an approximately 107-fold potency advantage over the benchmark sulfonamide acetazolamide...All complexes reduced MDA-MB-231 cell viability; among those with reliably determined IC50 values, complex 4 showed the greatest cytotoxicity (IC50 = 18.28 µM). These findings identify amide-linked Ir(III) complexes as highly potent LPO inhibitors with substituent-dependent inhibition modes."

Clinical • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Personalized Sequential Nephron Blockade for Diuretic Resistance in Acute Decompensated Heart Failure: A Narrative Review for the Cardiorenal Clinician. (PubMed, J Pers Med) - "We integrate contemporary randomized evidence with renal tubular physiology to propose a mechanism-based approach: acetazolamide for patients with hypochloremic metabolic alkalosis and enhanced proximal sodium reabsorption, thiazide-type diuretics when distal cotransporter escape predominates, vasopressin antagonists for dilutional hyponatremia complicating congestion, and sodium-glucose cotransporter 2 inhibitors as foundational therapy that combines modest acute natriuresis with durable cardiorenal protection...We propose a personalized, phenotype-driven framework in which early urinary sodium response, kidney function, serum chloride, acid-base status, serum sodium, background SGLT2 inhibitor therapy, and venous congestion imaging guide the selection, escalation, and de-escalation of adjunctive therapy, with the goal of more complete and safer decongestion in acute decompensated heart failure. Matching adjunct choice to a patient's individual biochemical..."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • Nephrology

Atypical Foster Kennedy Syndrome With Orbital Apex Involvement Secondary to Intracranial Meningiomatosis: A Case Report. (PubMed, Am J Case Rep) - "A conservative approach was used, including corticosteroids to reduce mass effect and acetazolamide to decrease intracranial pressure, aiming to preserve optic nerve function...Hormonal disturbances may have contributed to meningiomatosis development and growth, while orbital apex involvement suggests a complex mechanism beyond isolated optic nerve compression. Conservative management remains appropriate first-line therapy in multifocal disease with intracranial hypertension, with the goal of preserving visual function."

Journal • Brain Cancer • Cardiovascular • CNS Disorders • Endocrine Disorders • Hypertension • Meningioma • Ocular Inflammation • Oncology • Ophthalmology • Solid Tumor

Top advances of the year in autologous cellular therapy in melanoma and solid tumors. (PubMed, Cancer) - "Lifileucel, the first Food and Drug Administration-approved tumor-infiltrating lymphocyte (TIL) therapy for advanced melanoma, demonstrated durable efficacy in the 5-year analysis of the C-144-01 trial, with an objective response rate (ORR) of 31.4% and prolonged responses in a heavily pretreated population...Preferentially expressed antigen in melanoma (PRAME)-targeted T-cell receptor (TCR) T-cell therapy (anzu-cel, IMA203) showed promising activity in a phase 1 study, with ORR of approximately 50% in checkpoint inhibitor refractory melanoma, durable responses, and manageable toxicity, validating PRAME as a high value target across multiple tumor types...OBX-115, an IL-2 independent TIL platform expressing membrane-bound IL-15 regulated by acetazolamide, demonstrated early clinical activity with ORR of 67% in initial phase 1 data...Finally, afamitresgene autoleucel (afami-cel), a MAGE-A4 directed TCR-T therapy, showed durable efficacy in synovial sarcoma and expanding..."

Journal • Review • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • IL15 • MAGEA4 • PRAME

Multitargeted Anticancer Activities: Cathepsin B-Carbonic Anhydrase IX/XII Inhibitors Show Enhanced Cytotoxicity Against Lung Adenocarcinoma Cells. (PubMed, Arch Pharm (Weinheim)) - "Overall, respectively, three (KI < 25 nM) and two compounds (KI < 5.7 nM) showed better inhibition of hCA IX and XII as compared with reference drug acetazolamide. Compound 9f exhibited 35-fold and eightfold better hCA I/IX and hCA I/XII inhibition selectivity, respectively, as compared with SLC-0111. Likewise, all the synthesized compounds were also assayed for their inhibition profile against cathepsin B. Some compounds exhibited better inhibition of cathepsin B as compared with reference compound curcumin. In vitro cytotoxicity studies targeting non-cancerous Vero cells (green monkey kidney cells) and cancerous A549 cells (human lung adenocarcinoma cells) have also been performed, which showed interesting results."

Clinical • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CA9 • CTSB

High-Altitude Headache Resolving After Self-Administration of Goreisan: A Case Report. (PubMed, Cureus) - "Although improvement occurred temporally after Goreisan administration, spontaneous improvement or early acclimatization cannot be excluded, and causality cannot be established from this single case. This observation supports prospective evaluation of Goreisan in patients with HAH."

Journal • Cardiovascular • CNS Disorders • Hypertension • Migraine • Pain

Repeated transitions between intracranial hypotension and intracranial hypertension in Gorham-Stout disease: illustrative case. (PubMed, J Neurosurg Case Lessons) - "These observations suggest that CSF dynamics in skull base GSD may remain fragile despite successful leak repair and ongoing medical therapy. Early recognition and prolonged surveillance of intracranial pressure disturbances are essential, with timely escalation to medical or neurosurgical intervention to prevent irreversible neurological and visual morbidity. https://thejns.org/doi/10.3171/CASE26531."

Journal • Cardiovascular • CNS Disorders • Hypertension • Hypotension • Infectious Disease • Orthopedics • Pneumococcal Infections • Pneumonia

OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients (pts) with immune checkpoint inhibitor (ICI)–resistant advanced melanoma: Phase 1 results of the Agni-01 multicenter study. (ASCO 2025) - P1, P1/2 | "Funded by Obsidian Therapeutics Clinical Trial Registration Number: NCT06060613 Background: OBX-115 TIL are engineered to express mbIL15 regulated by the FDA-approved small-molecule drug acetazolamide (ACZ), abrogating the need for toxic high-dose IL2 after TIL infusion... Early data support clinical benefit (RP2D ORR 67%, DCR 100%) of OBX-115 regulatable engineered TIL cell therapy in the absence of IL2, including with outpatient low-dose LD. The safety profile is highly differentiated, without TRM, ICU transfer, or high-grade CRS. ACZ redosing is well-tolerated and offers an opportunity to deepen responses by inducing re-expression of mbIL15 on engrafted OBX-115 TIL, a unique capability among adoptive cell therapies."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • P1 data • Tumor-infiltrating lymphocyte • Heart Failure • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15 • IL6

OBX-115, an interleukin 2 (IL2)-sparing engineered tumor-infiltrating lymphocyte (TIL) cell therapy, in patients (pts) with immune checkpoint inhibitor (ICI)-resistant unresectable or metastatic melanoma. (ASCO 2024) - P1, P1/2 | "OBX-115 autologous engineered TIL cell therapy does not require co-administration of IL2 due to its regulatable expression of membrane-bound IL15 (mbIL15) using the FDA-approved small-molecule drug acetazolamide (ACZ) to provide cytokine support for TIL expansion and persistence...After lymphodepletion (cyclophosphamide, fludarabine), pts receive OBX-115 followed by ACZ once daily for up to 7 days; ACZ redosing (up to 7 days) is permitted at Wk 6 for non-responders... OBX-115regulatableengineeredTIL cell therapy was well-tolerated and produced consistently deepening and durable responses, indicating that OBX-115 may mediate CRs and durable clinical benefit in ICI-resistant metastatic melanoma without high-dose IL2. OBX-115 investigation continues in this and an ongoing Phase 1/2 multicenter study (NCT06060613)."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • Tumor-infiltrating lymphocyte • Hepatology • Melanoma • Oncology • Pain • Solid Tumor • CD69 • CD8 • ENTPD1 • IL15 • IL2 • PD-1

OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients with advanced melanoma that has progressed on/after immune checkpoint inhibitors (ICI): Phase 2 results. (ASCO 2026) - P1/2 | "Clinical Trial Registration Number: NCT06060613 Background: OBX-115 TIL are engineered to express mbIL15 under regulatory control of the small-molecule drug acetazolamide (ACZ); this engineering abrogates the need for toxic high-dose IL2 cytokine support after TIL infusion. OBX-115 TIL cell therapy at RP2D demonstrated encouraging efficacy in 2/3L advanced non-uveal melanoma, an area of unmet medical need. Unique aspects of the OBX-115 regimen, such as low-dose LD, ACZ-inducible mbIL15 expression, and CNB-enabled manufacturing, were associated with manageable side effects and compare favorably with other adoptive TIL approaches. Data support continued investigation of OBX-115 in the ongoing phase 2 portion of Agni-01 and planned registrational study."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • P2 data • Tumor-infiltrating lymphocyte • Eye Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15

A phase 1/2 study to investigate the safety and efficacy of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced solid tumors. (ASCO 2024) - P1, P1/2 | "OBX-115 TIL are engineered to express membrane-bound IL15 (mbIL15) under dose-dependent regulation using acetazolamide (ACZ), an FDA-approved small-molecule diuretic, avoiding the need for high-dose IL2...Cryopreserved OBX-115 is generated from the pt's own tumor tissue procured by surgical excision or core needle biopsy, and is infused after standard- (5 days) or low-dose (4 days) lymphodepletion (cyclophosphamide and fludarabine), based on clinical status...3. Creelan Nat Med 2021; Schoenfeld SITC 2021."

Clinical • IO biomarker • Metastases • P1/2 data • Tumor-infiltrating lymphocyte • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15

Efficacy of acetazolamide in adult sleep apnea: A systematic review of randomized controlled trials. (PubMed, Int Orthod) - "Acetazolamide may be a useful pharmacological adjunct for selected forms of SDB, particularly CSA and altitude-related ventilatory instability, and OSA patients seeking non-CPAP alternatives. Future large-scale, long-term trials are needed to optimize dosing and identify responder endotypes."

Journal • Review • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Tumor Microenvironment-Responsive Intelligent Hydrogel Co-Delivery System Enhances Ferroptosis for Triple-Negative Breast Cancer Therapy. (PubMed, Pharm Res) - "The TME-responsive PCG/ACZ/AA@HP-β-CD hydrogel integrates drug solubilization, intelligent delivery, and dual-mechanism enhancement. The combination of AA-induced ferroptosis via the HSP90/GPX4 axis and ACZ-mediated pH disruption represents a promising strategy for TNBC therapy with good biosafety."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDC37 • GPX4 • HSP90AA1

A randomized clinical trial of preventive acetazolamide therapy for acute mountain sickness in females compared to males (ERS 2026) - P4 | "AZA was effective in preventing AMS, with a number needed to treat between 8-11, and efficacy did not differ between sexes. Lower RRR and increased drug-related side effects with AZA in females, but similar ARR, require further investigations."

Clinical

Surgical Management of Lateral Sphenoid Recess Cerebrospinal Fluid Leak and Postoperative Bilateral Sigmoid Sinus Stenosis (AAO-HNSF 2026) - "Lumbar drain transduced at 40 cmH2O on postoperative day 2 and at 27 cmH2O after initiation of 500mg acetazolamide BID... CSF leaks in the lateral sphenoid recess can be managed endoscopically in most cases. Though atypical, sCSF-Ls can occur in nonobese individuals with normal opening pressures. This case highlights postoperative management of rebound intracranial hypertension and newly identified bilateral DVSS, with CT venography and venous manometry as cornerstones for diagnosis."

Cardiovascular • CNS Disorders • Hypertension • Obesity

Surgical Trends and Severity Implications of Migraine in Patients with Meniere's Disease: A Multicenter Study (AAO-HNSF 2026) - "Acetazolamide/betahistine use was higher across cohorts (RR=2.73, 1.55, 1.36, 1.12; all p≤0.006). In MD, comorbid migraines is linked to greater long-term medical, intratympanic, and rehabilitative therapy use without sustained increases in surgery, suggesting higher ongoing symptom burden rather than worse procedural outcomes."

Clinical • CNS Disorders • Migraine • Otorhinolaryngology