The fatty acid amide hydrolase and cyclooxygenase-inhibitory properties of novel amide derivatives of carprofen

Deplano, Alessandro (author)

Karlsson, Jessica, 1987- (author): Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)

Fowler, Christopher J. (author): Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)

Onnis, Valentina (author)

(creator_code:org_t)

Related links:: https://iris.unica.i...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

In experimental animals, inhibition of fatty acid amide hydrolase (FAAH) reduces the gastrointestinal damage produced by non-steroidal anti-inflammatory agents that act by inhibition of cyclooxygenase (COX). This suggests that compounds able to inhibit both enzymes may be potentially useful therapeutic agents. In the present study, we have investigated eight novel amide analogues of carprofen, ketoprofen and fenoprofen as potential FAAH/COX dual action inhibitors. Carpro-AM1 (2-(6-Chloro-9H-carbazol-2-yl)-N-(3-methylpyridin-2-yl)propenamide) and Carpro-AM6 (2-(6-Chloro-9H-carbazol-2-yl)-N-(3-chloropyridin-2-yl)propenamide) were found to be fully re-versible inhibitors of the hydrolysis of 0.5 mu M [H-3]anandamide in rat brain homogenates with IC50 values of 94 and 23 nM, respectively, i.e. 2-3 orders of magnitude more potent than carprofen in this respect. Both compounds inhibited the cyclooxygenation of arachidonic acid by ovine COX-1, and were more potent inhibitors of human recombinant COX-2 when 2-arachidonoylglycerol was used as substrate than when arachidonic acid was used. It is concluded that Carpro-AM1 and Carpro-AM6 are dual-acting FAAH/substrate-selective COX inhibitors.

By the author/editor: Deplano, Alessan ...; Karlsson, Jessic ...; Fowler, Christop ...; Onnis, Valentina

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

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