ArticleCNS neuroscience & therapeutics2016
Amiloride Analogs as ASIC1a Inhibitors.
Article in CNS neuroscience & therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Population Pharmacokinetics of Intranasal Amiloride in Healthy Volunteers.European journal of drug metabolism and pharmacokinetics · 2026Trial
- Acid-sensing ion channels as sensors of brain metabolic state.Pflugers Archiv : European journal of physiology · 2026Review
- Therapeutic Promise and Biotechnological Prospects ofInternational journal of molecular sciences · 2025Review
- ASIC1a mediated nucleus pulposus cells pyroptosis and glycolytic crosstalk as a molecular basis for intervertebral disc degeneration.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Inhibition of ASIC1a reduces ferroptosis in rheumatoid arthritis articular chondrocytes via the p53/NRF2/SLC7A11 pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Selective blockade of acid-sensing ion channel 1a can provide substantial hippocampal neuroprotection.Frontiers in cell and developmental biology · 2025Article
- The role of acid-sensing ion channels in monosodium urate-induced gouty pain in mice.Pflugers Archiv : European journal of physiology · 2024Article
- Inhibition of Acid-Sensing Ion Channels by KB-R7943, a Reverse NaBiomolecules · 2023Article
- Acid-sensing ion channel blocker diminazene facilitates proton-induced excitation of afferent nerves in a similar manner that NaFrontiers in cellular neuroscience · 2023Article
- Effects of Inhibitors of SLC9A-Type Sodium-Proton Exchangers onMolecular pharmacology · 2022Article
- Post-Ganglionic Sympathetic Neurons can Directly Sense Raised Extracellular NaFrontiers in physiology · 2022Article
- Development of ASIC1a ligand-gated ion channel drug screening assays across multiple automated patch clamp platforms.Frontiers in molecular neuroscience · 2022Article
- Mambalgin-2 Inhibits Lung Adenocarcinoma Growth and Migration by Selective Interaction With ASIC1/α-ENaC/γ-ENaC Heterotrimer.Frontiers in oncology · 2022Article
- ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain.eLife · 2021Article
- Extracellular Protons Mediate Presynaptic Homeostatic Potentiation at the Mouse Neuromuscular Junction.Neuroscience · 2021Article
- Neurodegenerative Disease: What Potential Therapeutic Role of Acid-Sensing Ion Channels?Frontiers in cellular neuroscience · 2021Review
- The Role of ASIC1a in Epilepsy: A Potential Therapeutic Target.Current neuropharmacology · 2021Review
- Protein Kinase C Regulates ASIC1a Protein Expression and Channel Function via NF-kB Signaling Pathway.Molecular neurobiology · 2020Article
- Mambalgin-2 Induces Cell Cycle Arrest and Apoptosis in Glioma Cells via Interaction with ASIC1a.Cancers · 2020Article
- Genetic Up-Regulation or Pharmacological Activation of the NaMolecular neurobiology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundASIC1a, the predominant acid-sensing ion channels (ASICs), is implicated in neurological disorders including stroke, traumatic spinal cord injury, and ALS. Potent ASIC1a inhibitors should have promising therapeutic potential for ASIC1a-related diseases.
aimsWe examined the inhibitory effects of a number of amiloride analogs on ASIC1a currents, aimed at understanding the structure-activity relationship and identifying potent ASIC1a inhibitors for stroke intervention.
methodsWhole-cell patch-clamp techniques and a mouse model of middle cerebral artery occlusion (MCAO)-induced focal ischemia were used. Surflex-Dock was used to dock the analogs into the pocket with default parameters.
resultsAmiloride and its analogs inhibit ASIC1a currents expressed in Chinese hamster ovary cells with a potency rank order of benzamil > phenamil > 5-(N,N-dimethyl)amiloride (DMA) > amiloride > 5-(N,N-hexamethylene)amiloride (HMA) ≥ 5-(N-methyl-N-isopropyl)amiloride (MIA) > 5-(N-ethyl-N-isopropyl)amiloride (EIPA). In addition, amiloride and its analogs inhibit ASIC currents in cortical neurons with the same potency rank order. In mice, benzamil and EIPA decreased MCAO-induced infarct volume. Similar to its effect on the ASIC current, benzamil showed a much higher potency than EIPA.
conclusionAddition of a benzyl group to the terminal guanidinyl group resulted in enhanced inhibitory activity on ASIC1a. On the other hand, the bulky groups added to the 5-amino residues slightly decreased the activity. Among the tested amiloride analogs, benzamil is the most potent ASIC1a inhibitor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.