ArticlePharmacological research2015
Peripheral FAAH and soluble epoxide hydrolase inhibitors are synergistically antinociceptive.
Article in Pharmacological research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- Novel dual inhibitor targeting FAAH and sEH: Design, synthesis, and in-vitro evaluation of oxadiazole analogues.Molecular diversity · 2026Article
- Polynitrogen-containing compounds as multi-target sEH/FAAH inhibitors: Structure-activity relationship and pharmacological studies.Bioorganic & medicinal chemistry · 2026Article
- Article
- Synthesis and evaluation of isoquinolinyl and pyridinyl-based dual inhibitors of fatty acid amide hydrolase and soluble epoxide hydrolase to alleviate orofacial hyperalgesia in the rat.Biochemistry and biophysics reports · 2025Article
- Structure-activity relationship studies and pharmacological evaluation of 4-phenylthiazoles as dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors.Bioorganic & medicinal chemistry · 2025Article
- Oleic acid released by sensory neurons inhibits TRPV1-mediated thermal hypersensitivity via GPR40.iScience · 2024Article
- Article
- 4-Phenyl-thiazole-based dual inhibitors of fatty acid amide hydrolase and soluble epoxide hydrolase do not alleviate orofacial inflammatory pain in female rats.BBA advances · 2024Article
- URB937 Prevents the Development of Mechanical Allodynia in Male Rats with Trigeminal Neuralgia.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Structure-activity relationship studies of benzothiazole-phenyl analogs as multi-target ligands to alleviate pain without affecting normal behavior.Prostaglandins & other lipid mediators · 2023Article
- Lysophosphatidylcholine: Potential Target for the Treatment of Chronic Pain.International journal of molecular sciences · 2022Review
- Soluble Epoxide Hydrolase and Diabetes Complications.International journal of molecular sciences · 2022Review
- Polypharmacological Approaches for CNS Diseases: Focus on Endocannabinoid Degradation Inhibition.Cells · 2022Review
- Further exploration of the structure-activity relationship of dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors.Bioorganic & medicinal chemistry · 2021Article
- The Peripheral Cannabinoid Receptor Type 1 (CBMolecules (Basel, Switzerland) · 2021Review
- The endocannabinoid system - current implications for drug development.Journal of internal medicine · 2021Review
- Discovery of Soluble Epoxide Hydrolase Inhibitors from Chemical Synthesis and Natural Products.Journal of medicinal chemistry · 2021Review
- Inhibition of the Soluble Epoxide Hydrolase as an Analgesic Strategy: A Review of Preclinical Evidence.Journal of pain research · 2021Review
- Article
- Lack of rewarding effects of a soluble epoxide hydrolase inhibitor TPPU in mice: Comparison with morphine.Neuropsychopharmacology reports · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
We need better medicines to control acute and chronic pain. Fatty acid amide hydrolase (FAAH) and soluble epoxide hydrolase (sEH) catalyze the deactivating hydrolysis of two classes of bioactive lipid mediators--fatty acid ethanolamides (FAEs) and epoxidized fatty acids (EpFAs), respectively--which are biogenetically distinct but share the ability to attenuate pain responses and inflammation. In these experiments, we evaluated the antihyperalgesic activity of small-molecule inhibitors of FAAH and sEH, administered alone or in combination, in two pain models: carrageenan-induced hyperalgesia in mice and streptozocin-induced allodynia in rats. When administered separately, the sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea (TPPU) and the peripherally restricted FAAH inhibitor URB937 were highly active in the two models. The combination TPPU plus URB937 was markedly synergistic, as assessed using isobolographic analyses. The results of these experiments reveal the existence of a possible functional crosstalk between FAEs and EpFAs in regulating pain responses. Additionally, the results suggest that combinations of sEH and FAAH inhibitors might be exploited therapeutically to achieve greater analgesic efficacy.
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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.