ArticleThe Journal of pharmacology and experimental therapeutics2009
Synergy between enzyme inhibitors of fatty acid amide hydrolase and cyclooxygenase in visceral nociception.
Article in The Journal of pharmacology and experimental therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 114 citations in OpenAlex.
- Synthesis Methods and Therapeutic Journey of Carprofen and Its Derivatives: A Review.Chemical biology & drug design · 2025Review
- Visceral Pain in Preterm Infants with Necrotizing Enterocolitis: Underlying Mechanisms and Implications for Treatment.Paediatric drugs · 2025Review
- Combined Endocannabinoid and Cyclooxygenase Inhibition Additively Attenuates Post-Surgical Pain.Cannabis and cannabinoid research · 2025Article
- Identification and evaluation of a pinocembrin analog as a TRPV1 inhibitor with analgesic properties in murine pain models.Frontiers in pharmacology · 2025Article
- FAAH inhibitor URB597 shows anti-hyperalgesic action and increases brain and intestinal tissues fatty acid amides in a model of CRFNeurogastroenterology and motility · 2024Article
- Assessment of NSAIDs as potential inhibitors of the fatty acid amide hydrolase I (FAAH-1) using three different primary fatty acid amide substrates in vitro.BMC pharmacology & toxicology · 2022Article
- Design, synthesis andJournal of enzyme inhibition and medicinal chemistry · 2021Article
- The endocannabinoid system - current implications for drug development.Journal of internal medicine · 2021Review
- Behavioral Battery for Testing Candidate Analgesics in Mice. II. Effects of Endocannabinoid Catabolic Enzyme Inhibitors and ∆9-Tetrahydrocannabinol.The Journal of pharmacology and experimental therapeutics · 2021Article
- Exploring the fatty acid amide hydrolase and cyclooxygenase inhibitory properties of novel amide derivatives of ibuprofen.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Non-opioid Analgesics and the Endocannabinoid SystemBalkan medical journal · 2020Article
- Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?International journal of molecular sciences · 2020Review
- Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain.International journal of molecular sciences · 2020Review
- Role of epoxy-fatty acids and epoxide hydrolases in the pathology of neuro-inflammation.Biochimie · 2019Review
- CBPharmacology, biochemistry, and behavior · 2019Article
- The monoacylglycerol lipase inhibitor KML29 with gabapentin synergistically produces analgesia in mice.British journal of pharmacology · 2017Article
- Highly selective CBNaunyn-Schmiedeberg's archives of pharmacology · 2017Article
- MAGL inhibition modulates gastric secretion and motility following NSAID exposure in mice.European journal of pharmacology · 2017Article
- Pharmacological inhibition of soluble epoxide hydrolase or genetic deletion reduces diclofenac-induced gastric ulcers.Life sciences · 2017Article
- Naproxen and Diclofenac Attenuate Atorvastatin-induced Preconditioning of the Myocardium.Cureus · 2017Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The present study investigated whether inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for anandamide catabolism, produces antinociception in the acetic acid-induced abdominal stretching model of visceral nociception. Genetic deletion or pharmacological inhibition of FAAH reduced acetic acid-induced abdominal stretching. Transgenic mice that express FAAH exclusively in the nervous system displayed the antinociceptive phenotype, indicating the involvement of peripheral fatty acid amides. The cannabinoid receptor 1 (CB(1)) receptor antagonist, rimonabant, but not the cannabinoid receptor 2 (CB(2)) receptor antagonist, SR144528, blocked the antinociceptive phenotype of FAAH(-/-) mice and the analgesic effects of URB597 (3'-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate) or OL-135 (1-oxo-1[5-(2-pyridyl)-2-yl]-7-phenyl heptane), respective irreversible and reversible FAAH inhibitors, administered to C57BL/6 mice. The opioid receptor antagonist, naltrexone, did not block the analgesic effects of either FAAH inhibitor. URB597, ED(50) [95% confidence interval (CI) = 2.1 (1.5-2.9) mg/kg], and the nonselective cyclooxygenase inhibitor, diclofenac sodium [ED(50) (95% CI) = 9.8 (8.2-11.7) mg/kg], dose-dependently inhibited acetic acid-induced abdominal stretching. Combinations of URB597 and diclofenac yielded synergistic analgesic interactions according to isobolographic analysis. It is important that FAAH(-/-) mice and URB597-treated mice displayed significant reductions in the severity of gastric irritation caused by diclofenac. URB597 lost its gastroprotective effects in CB(1)(-/-) mice, whereas it maintained its efficacy in CB(2)(-/-) mice, indicating a CB(1) mechanism of action. Taken together, the results of the present study suggest that FAAH represents a promising target for the treatment of visceral pain, and a combination of FAAH inhibitors and NSAIDs may have great utility to treat visceral pain, with reduced gastric toxicity.
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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.