Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.

<h4>Background</h4>In addition to their effects upon prostaglandin synthesis, the non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) by cyclooxygenase-2 (COX-2) and fatty acid...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jessica Karlsson, Christopher J Fowler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1db7299895194df0a2f0588f105e5648
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1db7299895194df0a2f0588f105e5648
record_format	dspace
spelling	oai:doaj.org-article:1db7299895194df0a2f0588f105e56482021-11-25T06:07:07ZInhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.1932-620310.1371/journal.pone.0103589https://doaj.org/article/1db7299895194df0a2f0588f105e56482014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25061885/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>In addition to their effects upon prostaglandin synthesis, the non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) by cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH), respectively. Here, we investigated whether these effects upon endocannabinoid metabolism are shared by the main metabolites of ibuprofen and flurbiprofen.<h4>Methodology/principal findings</h4>COX activities were measured via changes in oxygen consumption due to oxygenation of arachidonic acid (for COX-1) and arachidonic acid and 2-AG (for COX-2). FAAH activity was quantified by measuring hydrolysis of tritium labelled AEA in rat brain homogenates. The ability of ibuprofen and flurbiprofen to inhibit COX-2-catalysed oxygenation of 2-AG at lower concentrations than the oxygenation of arachidonic acid was seen with 4'-hydroxyflurbiprofen and possibly also 3'-hydroxyibuprofen, albeit at lower potencies than the parent compounds. All ibuprofen and flurbiprofen metabolites retained the ability to inhibit FAAH in a pH-dependent manner, although the potency was lower than seen with the parent compounds.<h4>Conclusions/significance</h4>It is concluded that the primary metabolites of ibuprofen and flurbiprofen retain some of the properties of the parent compound with respect to inhibition of endocannabinoid metabolism. However, these effects are unlikely to contribute to the actions of the parent compounds in vivo.Jessica KarlssonChristopher J FowlerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e103589 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jessica Karlsson Christopher J Fowler Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.
description	<h4>Background</h4>In addition to their effects upon prostaglandin synthesis, the non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) by cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH), respectively. Here, we investigated whether these effects upon endocannabinoid metabolism are shared by the main metabolites of ibuprofen and flurbiprofen.<h4>Methodology/principal findings</h4>COX activities were measured via changes in oxygen consumption due to oxygenation of arachidonic acid (for COX-1) and arachidonic acid and 2-AG (for COX-2). FAAH activity was quantified by measuring hydrolysis of tritium labelled AEA in rat brain homogenates. The ability of ibuprofen and flurbiprofen to inhibit COX-2-catalysed oxygenation of 2-AG at lower concentrations than the oxygenation of arachidonic acid was seen with 4'-hydroxyflurbiprofen and possibly also 3'-hydroxyibuprofen, albeit at lower potencies than the parent compounds. All ibuprofen and flurbiprofen metabolites retained the ability to inhibit FAAH in a pH-dependent manner, although the potency was lower than seen with the parent compounds.<h4>Conclusions/significance</h4>It is concluded that the primary metabolites of ibuprofen and flurbiprofen retain some of the properties of the parent compound with respect to inhibition of endocannabinoid metabolism. However, these effects are unlikely to contribute to the actions of the parent compounds in vivo.
format	article
author	Jessica Karlsson Christopher J Fowler
author_facet	Jessica Karlsson Christopher J Fowler
author_sort	Jessica Karlsson
title	Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.
title_short	Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.
title_full	Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.
title_fullStr	Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.
title_full_unstemmed	Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.
title_sort	inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/1db7299895194df0a2f0588f105e5648
work_keys_str_mv	AT jessicakarlsson inhibitionofendocannabinoidmetabolismbythemetabolitesofibuprofenandflurbiprofen AT christopherjfowler inhibitionofendocannabinoidmetabolismbythemetabolitesofibuprofenandflurbiprofen
_version_	1718414150200197120

Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.

Ejemplares similares