The ability of a series of homologues and analogues of palmitoylethanolamide to inhibit the uptake and fatty acid amidohydrolase (FAAH)‐catalysed hydrolysis of [3H]‐anandamide ([3H]‐AEA) has been investigated. Palmitoylethanolamide and homologues with chain lengths from 12–18 carbon atoms inhibited rat brain [3H]‐AEA metabolism with pI50 values of ∼5. Homologues with chain lengths eight carbon atoms gave <20% inhibition at 100 μM. R‐palmitoyl‐(2‐methyl)ethanolamide, palmitoylisopropylamide and oleoylethanolamide inhibited [3H]‐AEA metabolism with pI50 values of 5.39 (competitive inhibition), 4.89 (mixed type inhibition) and 5.33 (mixed type inhibition), respectively. With the exception of oleoylethanolamide, the compounds did not produce dramatic inhibition of [3H]‐WIN 55,212‐2 binding to human CB2 receptors expressed on CHO cells. Palmitoylethanolamide, palmitoylisopropylamide and R‐palmitoyl‐(2‐methyl)ethanolamide had modest effects upon [3H]‐CP 55,940 binding to human CB1 receptors expressed on CHO cells. Most of the compounds had little effect upon the uptake of [3H]‐AEA into C6 and/or RBL‐2H3 cells. However, palmitoylcyclohexamide (100 μM) and palmitoylisopropylamide (30 and 100 μM) produced more inhibition of [3H]‐AEA uptake than expected to result from inhibition of [3H]‐AEA metabolism alone. In intact C6 cells, palmitoylisopropylamide and oleoylethanolamide inhibited formation of [3H]‐ethanolamine from [3H]‐AEA to a similar extent as AM404, whereas palmitoylethanolamide, palmitoylcyclohexamide and R‐palmitoyl‐(2‐methyl)ethanolamide were less effective. These data provide useful information upon the ability of palmitoylethanolamide analogues to act as ‘entourage’ compounds. Palmitoylisopropylamide may prove useful as a template for design of compounds that reduce the cellular accumulation and metabolism of AEA without affecting either CB1 or CB2 receptors.
British Journal of Pharmacology – Wiley
Published: Jan 1, 2001
Keywords: ; ;
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera