Inhibition of FAAH, TRPV1, and COX2 by NSAID-serotonin conjugates

Bioorg Med Chem Lett. 2014 Dec 15;24(24):5695-5698. doi: 10.1016/j.bmcl.2014.10.064. Epub 2014 Oct 28.

Abstract

Serotonin was linked by amidation to the carboxylic acid groups of a series of structurally diverse NSAIDs. The resulting NSAID-serotonin conjugates were tested in vitro for their ability to inhibit FAAH, TRPV1, and COX2. Ibuprofen-5-HT and Flurbiprofen-5-HT inhibited all three targets with approximately the same potency as N-arachidonoyl serotonin (AA-5-HT), while Fenoprofen-5-HT and Naproxen-5-HT showed activity as dual inhibitors of TRPV1 and COX2.

Keywords: Arachidonoyl serotonin; Dual inhibition; FAAH; Fatty acid amide hydrolase; Multimodal inhibition; NSAID; TRPV1; Transient receptor potential vanilloid type 1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amidohydrolases / antagonists & inhibitors*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cyclooxygenase 2 / chemistry*
  • Flurbiprofen / chemistry
  • Flurbiprofen / metabolism
  • Humans
  • Serotonin / chemistry*
  • Serotonin / metabolism
  • TRPV Cation Channels / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Serotonin
  • Flurbiprofen
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Amidohydrolases
  • fatty-acid amide hydrolase