ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Dual modulation of endocannabinoid transport and fatty acid amide hydrolase protects against excitotoxicity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. 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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Who cites it
48 citing papers in PubMed, 124 citations in OpenAlex.
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- Synaptic control of retinal ganglion cell survival and axon regeneration.Molecular neurodegeneration · 2026Review
- Anti-Inflammatory Effects of Cannabinoids in Therapy of Neurodegenerative Disorders and Inflammatory Diseases of the CNS.International journal of molecular sciences · 2025Review
- Cannabinoid Analgesia in Postoperative Pain Management: From Molecular Mechanisms to Clinical Reality.International journal of molecular sciences · 2024Review
- A regio- and stereoselective Heck-Matsuda process for construction of γ-aryl allylsulfonyl fluorides.RSC advances · 2022Article
- On the Biomedical Properties of Endocannabinoid Degradation and Reuptake Inhibitors: Pre-clinical and Clinical Evidence.Neurotoxicity research · 2021Review
- Copper-Promoted Conjugate Addition of Carboxylic Acids to Ethenesulfonyl Fluoride (ESF) for Constructing Aliphatic Sulfonyl Fluorides.ACS omega · 2021Article
- Excitotoxic stimulation activates distinct pathogenic and protective expression signatures in the hippocampus.Journal of cellular and molecular medicine · 2021Article
- Experimental Therapeutic Strategies in Epilepsies Using Anti-Seizure Medications.Journal of experimental pharmacology · 2021Review
- Early Synaptic Alterations and Selective Adhesion Signaling in Hippocampal Dendritic Zones Following Organophosphate Exposure.Scientific reports · 2019Article
- Cannabinoid Receptor Type 1 Agonist ACEA Improves Cognitive Deficit on STZ-Induced Neurotoxicity Through Apoptosis Pathway and NO Modulation.Neurotoxicity research · 2019Article
- Neuroprotective Effect of AM404 Against NMDA-Induced Hippocampal Excitotoxicity.Frontiers in cellular neuroscience · 2019Article
- Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures.Metabolic brain disease · 2018Article
- The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration.Frontiers in neuroscience · 2018Review
- AM404, paracetamol metabolite, prevents prostaglandin synthesis in activated microglia by inhibiting COX activity.Journal of neuroinflammation · 2017Article
- Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration.Brain sciences · 2017Article
- Inhibitor of Endocannabinoid Deactivation Protects Against In Vitro and In Vivo Neurotoxic Effects of Paraoxon.Journal of molecular neuroscience : MN · 2017Article
- Clinical studies and anti-inflammatory mechanisms of treatments.Epilepsia · 2017Article
- Sulfur - fluorine bond in PET radiochemistry.EJNMMI radiopharmacy and chemistry · 2017Review
- Blast waves from detonated military explosive reduce GluR1 and synaptophysin levels in hippocampal slice cultures.Experimental neurology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The endocannabinoid system has been suggested to elicit signals that defend against several disease states including excitotoxic brain damage. Besides direct activation with CB1 receptor agonists, cannabinergic signaling can be modulated through inhibition of endocannabinoid transport and fatty acid amide hydrolase (FAAH), two mechanisms of endocannabinoid inactivation. To test whether the transporter and FAAH can be targeted pharmacologically to modulate survival/repair responses, the transport inhibitor N-(4-hydroxyphenyl)-arachidonamide (AM404) and the FAAH inhibitor palmitylsulfonyl fluoride (AM374) were assessed for protection against excitotoxicity in vitro and in vivo. AM374 and AM404 both enhanced mitogen-activated protein kinase (MAPK) activation in cultured hippocampal slices. Interestingly, combining the distinct inhibitors produced additive effects on CB1 signaling and associated neuroprotection. After an excitotoxic insult in the slices, infusing the AM374/AM404 combination protected against cytoskeletal damage and synaptic decline, and the protection was similar to that produced by the stable CB1 agonist AM356 (R-methanandamide). AM374/AM404 and the agonist also elicited cytoskeletal and synaptic protection in vivo when coinjected with excitotoxin into the dorsal hippocampus. Correspondingly, potentiating endocannabinoid responses with the AM374/AM404 combination prevented behavioral alterations and memory impairment that are characteristic of excitotoxic damage. The protective effects mediated by AM374/AM404 were (1) evident 7 d after insult, (2) correlated with the preservation of CB1-linked MAPK signaling, and (3) were blocked by a selective CB1 antagonist. These results indicate that dual modulation of the endocannabinoid system with AM374/AM404 elicits neuroprotection through the CB1 receptor. The transporter and FAAH are modulatory sites that may be exploited to enhance cannabinergic signaling for therapeutic purposes.
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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.