Inhibitory properties of ibuprofen and its amide analogues towards the hydrolysis and cyclooxygenation of the endocannabinoid anandamide
2013 (English)In: Journal of enzyme inhibition and medicinal chemistry (Print), ISSN 1475-6366, E-ISSN 1475-6374, Vol. 28, no 1, 172-182 p.Article in journal (Refereed) Published
A dual-action cyclooxygenase (COX)-fatty acid amide hydrolase (FAAH) inhibitor may have therapeutic usefulness as an analgesic, but a key issue is finding the right balance of inhibitory effects. This can be done by the design of compounds exhibiting different FAAH/COX-inhibitory potencies. In the present study, eight ibuprofen analogues were investigated. Ibuprofen (1), 2-(4-Isobutylphenyl)-N-(2-(3-methylpyridin-2-ylamino)-2-oxoethyl)propanamide (9) and N-(3-methylpyridin-2-yl)-2-(4'-isobutylphenyl) propionamide (2) inhibited FAAH with IC50 values of 134, 3.6 and 0.52 mu M respectively. The corresponding values for COX-1 were similar to 29, similar to 50 and similar to 60 mu M, respectively. Using arachidonic acid as substrate, the compounds were weak inhibitors of COX-2. However, when anandamide was used as COX-2 substrate, potency increased, with approximate IC50 values of similar to 6, similar to 10 and similar to 19 mu M, respectively. Compound 2 was confirmed to be active in vivo in a murine model of visceral nociception, but the effects of the compound were not blocked by CB receptor antagonists.
Place, publisher, year, edition, pages
2013. Vol. 28, no 1, 172-182 p.
Fatty acid amide hydrolase, cyclooxygenase, ibuprofen, analgesia, cannabinoid
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:umu:diva-66785DOI: 10.3109/14756366.2011.643304ISI: 000313663400022OAI: oai:DiVA.org:umu-66785DiVA: diva2:610610