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Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide

  1. Kent-Olov Jonsson1,*,
  2. Séverine Vandevoorde2,
  3. Didier M Lambert2,
  4. Gunnar Tiger1,
  5. Christopher J Fowler1

Article first published online: 29 JAN 2009

DOI: 10.1038/sj.bjp.0704199

Issue

British Journal of Pharmacology

British Journal of Pharmacology

Volume 133, Issue 8, pages 1263–1275, August 2001

Additional Information

How to Cite

Jonsson, K.-O., Vandevoorde, S., Lambert, D. M., Tiger, G. and Fowler, C. J. (2001), Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide. British Journal of Pharmacology, 133: 1263–1275. doi: 10.1038/sj.bjp.0704199

Author Information

  1. 1

    Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87 Umeå, Sweden

  2. 2

    Unité de Chimie pharmaceutique et de Radiopharmacie, Université catholique de Louvain, Avenue Mounier, 73, UCL-CMFA 73.40, B-1200 Brussels, Belgium

*Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87 Umeå, Sweden. E-mail: Kentolov.Jonsson@pharm.umu.se

Publication History

  1. Issue published online: 29 JAN 2009
  2. Article first published online: 29 JAN 2009
  3. (Received March 5, 2001, Revised May 31, 2001, Accepted June 4, 2001)

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Keywords:

  • Anandamide;
  • fatty acid amidohydrolase;
  • palmitoylethanolamide

  • 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 leqslant R: less-than-or-eq, slanteight 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 (2001) 133, 1263–1275; doi:10.1038/sj.bjp.0704199

View Full Article (HTML) Get PDF (315K)