title: Inhibition of FAAH, TRPV1, and COX2 by NSAID-serotonin conjugates.
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.
authors.affiliation: Roseman University of Health Sciences, College of Pharmacy, 10920 South River Front Parkway, South Jordan, UT 84095, USA. Electronic address: trose@roseman.edu.
authors.forename: Tyler M
authors.initials: TM
authors.lastname: Rose
authors.affiliation: University of Utah, College of Pharmacy, Department of Pharmacology and Toxicology, Salt Lake City, UT 84112, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Reilly
authors.affiliation: University of Utah, College of Pharmacy, Department of Pharmacology and Toxicology, Salt Lake City, UT 84112, USA.
authors.forename: Cassandra E
authors.initials: CE
authors.lastname: Deering-Rice
authors.affiliation: Roseman University of Health Sciences, College of Pharmacy, 10920 South River Front Parkway, South Jordan, UT 84095, USA.
authors.forename: Clinton
authors.initials: C
authors.lastname: Brewster
authors.affiliation: Roseman University of Health Sciences, College of Pharmacy, 10920 South River Front Parkway, South Jordan, UT 84095, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Brewster
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000737:chemistry*; D005480:Flurbiprofen / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D012701:Serotonin / Q000737:chemistry* / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000894:Anti-Inflammatory Agents, Non-Steroidal; D051546:Cyclooxygenase 2; D005480:Flurbiprofen; D012701:Serotonin; D050916:TRPV Cation Channels; D000099252:Fatty Acid Amide Hydrolases; C494482:TRPV1 protein, human; C496540:PTGS2 protein, human
keywords: Arachidonoyl serotonin; Dual inhibition; FAAH; Fatty acid amide hydrolase; Multimodal inhibition; NSAID; TRPV1; Transient receptor potential vanilloid type 1