Online citations, reference lists, and bibliographies.
← Back to Search

Acidic Nonsteroidal Anti-inflammatory Drugs Inhibit Rat Brain Fatty Acid Amide Hydrolase In A PH-dependent Manner

C. Fowler, S. Holt, G. Tiger
Published 2003 · Medicine, Chemistry

Cite This
Download PDF
Analyze on Scholarcy
Share
Previous studies have demonstrated that fatty acid amide hydrolase, the enzyme responsible for the metabolism of anandamide, is inhibited by the acidic non-steroidal anti-inflammatory drug (NSAID) ibuprofen with a potency that increases as the assay pH is reduced. Here we show that (R) -, (S) - and (R, S) -flurbiprofen, indomethacin and niflumic acid show similar pH-dependent shifts in potency to that seen with ibuprofen. Thus, (S) -flurbiprofen inhibited 2 μM [3 H]anandamide metabolism with IC 50 values of 13 and 50 μM at assay pH values of 6 and 8, respectively. In contrast, the neutral compound celecoxib was a weak fatty acid amide hydrolase inhibitor and showed no pH dependency (IC 50 values ~300 μM at both assay pH). The cyclooxygenase-2-selective inhibitors nimesulide and SC-58125 did not inhibit fatty acid amide hydrolase activity at either pH. The data are consistent with the conclusion that the non-ionised forms of the acidic NSAIDs are responsible for the inhibition of fatty acid amide hydrolase.
This paper references



This paper is referenced by
10.1038/sj.bjp.0707352
Interaction of ligands for the peroxisome proliferator‐activated receptor γ with the endocannabinoid system
A. Lenman (2007)
10.1016/J.CHEMBIOL.2007.05.014
Endocannabinoids and related compounds: walking back and forth between plant natural products and animal physiology.
V. Di Marzo (2007)
10.1111/j.1476-5381.2010.00703.x
Effects of COX‐2 inhibition on spinal nociception: the role of endocannabinoids
L. E. Staniaszek (2010)
Identification and characterization of carprofen as a multi-target FAAH / COX inhibitor
Angelo D. Favia (2013)
10.3923/IJP.2016.812.820
Role of PPARα and PPARγ in Mediating the Analgesic Properties of Ibuprofen in vivo and the Effects of Dual PPARα/γ Activation in Inflammatory Pain Model in the Rat
M. Alsalem (2016)
10.1111/j.1476-5381.2008.00029.x
The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1
C. Fowler (2009)
10.2165/11585260-000000000-00000
Role of Cannabinoids in the Treatment of Pain and (Painful) Spasticity
M. Karst (2012)
10.1016/j.imbio.2009.12.005
Cannabinoids and the immune system: an overview.
R. Tanasescu (2010)
10.1016/j.tips.2012.05.003
NSAIDs: eNdocannabinoid stimulating anti-inflammatory drugs?
C. Fowler (2012)
10.1016/j.pbb.2005.01.023
The endocannabinoid signaling system: Pharmacological and therapeutic aspects
C. Fowler (2005)
10.1007/978-0-387-74349-3_3
Removal of Endocannabinoids by the Body: Mechanisms and Therapeutic Possibilities
C. Fowler (2008)
10.1016/J.PHRS.2006.07.006
The potency of the fatty acid amide hydrolase inhibitor URB597 is dependent upon the assay pH.
Ben Paylor (2006)
10.7282/T3X350PC
Chemical-induced alterations in the endocannabinoid system in mouse skin
Irene M. Wohlman (2016)
10.1517/13543780802691951
Cannabinoids against pain. Efficacy and strategies to reduce psychoactivity: a clinical perspective
M. Karst (2009)
10.1007/978-3-7091-0888-8
Nerve-Driven Immunity
M. Levite (2012)
10.1186/ar2401
Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis
D. Richardson (2008)
10.1021/jm3011146
Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor.
Angelo D. Favia (2012)
Endocannabinoid metabolism : the impact of inflammatory factors and pharmacological inhibitors
Jessica Karlsson (2018)
10.1038/sj.bjp.0707433
Endocannabinoid metabolism and uptake: novel targets for neuropathic and inflammatory pain
M. Jhaveri (2007)
10.1007/s12035-007-0001-6
The Pharmacology of the Cannabinoid System—A Question of Efficacy and Selectivity
C. Fowler (2007)
10.1124/jpet.110.168831
Cyclooxygenase-2 Mediates Anandamide Metabolism in the Mouse Brain
S. Glaser (2010)
10.1055/s-0028-1083094
Schmerzlinderung durch Cannabinoide? – Bedeutung des Endocannabinoidsystems und der Cannabinoide für die Schmerztherapie
M. Karst (2008)
10.2174/156802608783498005
Overview of the chemical families of fatty acid amide hydrolase and monoacylglycerol lipase inhibitors.
S. Vandevoorde (2008)
10.1016/j.ejmech.2010.04.040
Chemistry around imidazopyrazine and ibuprofen: discovery of novel fatty acid amide hydrolase (FAAH) inhibitors.
Frédéric De Wael (2010)
10.1007/3-540-26573-2_6
Modulators of endocannabinoid enzymic hydrolysis and membrane transport.
W. Ho (2005)
10.1038/sj.bjp.0707456
The complications of promiscuity: endocannabinoid action and metabolism
S. Alexander (2007)
10.2174/1874467210902010001
Mechanisms of non-opioid analgesics beyond cyclooxygenase enzyme inhibition.
M. Hamza (2009)
10.1016/J.EJPHAR.2007.02.051
Inhibition of fatty acid amide hydrolase, a key endocannabinoid metabolizing enzyme, by analogues of ibuprofen and indomethacin.
S. Holt (2007)
10.1016/J.JBBM.2004.04.020
A simple stopped assay for fatty acid amide hydrolase avoiding the use of a chloroform extraction phase.
L. Boldrup (2004)
Pharmacology of Palmitoylethanolamide and Related Compounds
Kent-Olov Jonsson (2005)
10.1007/978-3-540-88955-7_1
The life cycle of the endocannabinoids: formation and inactivation.
S. Alexander (2009)
10.1016/j.bmcl.2014.10.064
Inhibition of FAAH, TRPV1, and COX2 by NSAID-serotonin conjugates.
Tyler M. Rose (2014)
See more
Semantic Scholar Logo Some data provided by SemanticScholar