ArticleBritish journal of pharmacology2009
Disruption of nNOS-PSD95 protein-protein interaction inhibits acute thermal hyperalgesia and chronic mechanical allodynia in rodents.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
48 citing papers in PubMed, 105 citations in OpenAlex.
- Tat-NR2B9c prevent cognitive dysfunction in mice modeling Alzheimer's Disease induced by AβIBRO neuroscience reports · 2025Article
- PSD-95 Protein: A Promising Therapeutic Target in Chronic Pain.Molecular neurobiology · 2025Review
- Agmatine inhibits NMDA receptor-mediated calcium transients in mouse spinal cord dorsal horn via intact PSD95-nNOS signaling.The Journal of pharmacology and experimental therapeutics · 2024Article
- Post-stroke effects of IC87201 on neurobehavioral function and brain injuries: A stereological study.IBRO neuroscience reports · 2024Article
- The IC87201 (a PSD95/nNOS Inhibitor) Attenuates Post- Stroke Injuries.Neurochemical research · 2024Article
- Neuronal Nitric Oxide Synthase and Post-Translational Modifications in the Development of Central Nervous System Diseases: Implications and Regulation.Molecules (Basel, Switzerland) · 2023Review
- Targeting the nitric oxide/cGMP signaling pathway to treat chronic pain.Neural regeneration research · 2023Review
- Inhibition of PSD95-nNOS protein-protein interactions decreases morphine reward and relapse vulnerability in rats.Addiction biology · 2022Article
- Bidirectional protein-protein interactions control liquid-liquid phase separation of PSD-95 and its interaction partners.iScience · 2022Article
- NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain.Frontiers in cellular neuroscience · 2022Review
- Targeting PSD95/nNOS by ZL006 alleviates social isolation-induced heightened attack behavior in mice.Psychopharmacology · 2022Article
- A Compound Mitigates Cancer Pain and Chemotherapy-Induced Neuropathic Pain by Dually Targeting nNOS-PSD-95 Interaction and GABANeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- A pain killer without analgesic tolerance designed by co-targeting PSD-95-nNOS interaction and α2-containning GABATheranostics · 2021Article
- Targeting receptor complexes: a new dimension in drug discovery.Nature reviews. Drug discovery · 2020Review
- Fenamates Inhibit Human Sodium Channel Nav1.2 and Protect Glutamate-Induced Injury in SH-SY5Y Cells.Cellular and molecular neurobiology · 2020Article
- Modeling rapid and selective capture of nNOS-PSD-95 uncouplers from Sanhuang Xiexin decoction by novel molecularly imprinted polymers based on metal-organic frameworks.RSC advances · 2020Article
- PDZ Domains as Drug Targets.Advanced therapeutics · 2019Review
- Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition.International review of cell and molecular biology · 2019Review
- Neuronal nitric oxide synthase and affective disorders.IBRO reports · 2018Review
- Disrupting interaction of PSD-95 with nNOS attenuates hemorrhage-induced thalamic pain.Neuropharmacology · 2018Article
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
background and purposePost-synaptic density protein 95 (PSD95) contains three PSD95/Dosophilia disc large/ZO-1 homology domains and links neuronal nitric oxide synthase (nNOS) with the N-methyl-D-aspartic acid (NMDA) receptor. This report assesses the effects of disruption of the protein-protein interaction between nNOS and PSD95 on pain sensitivity in rodent models of hyperalgesia and neuropathic pain. EXPERIMENTAL APPROACH: We generated two molecules that interfered with the nNOS-PSD95 interaction: IC87201, a small molecule inhibitor; and tat-nNOS (residues 1-299), a cell permeable fusion protein containing the PSD95 binding domain of nNOS. We then characterized these inhibitors using in vitro and in vivo models of acute hyperalgesia and chronic allodynia, both of which are thought to require nNOS activation. KEY
resultsIC87201 and tat-nNOS (1-299) inhibited the in vitro binding of nNOS with PSD95, without inhibiting nNOS catalytic activity. Both inhibitors also blocked NMDA-induced 3',5'-cyclic guanosine monophosphate (cGMP) production in primary hippocampal cultures. Intrathecal administration of either inhibitor potently reversed NMDA-induced thermal hyperalgesia in mice. At anti-hyperalgesic doses, there was no effect on acute pain thresholds or motor coordination. Intrathecal administration of IC87201 and tat-nNOS also reversed mechanical allodynia induced by chronic constriction of the sciatic nerve. CONCLUSIONS AND IMPLICATIONS: nNOS-PSD95 interaction is important in maintaining hypersensitivity in acute and chronic pain. Disruption of the nNOS-PSD95 interaction provides a novel approach to obtain selective anti-hyperalgesic compounds.
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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.