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The Potential of Inhibitors of Endocannabinoid Metabolism for Drug Development: A Critical Review

  • Christopher J. FowlerEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 231)

Abstract

The endocannabinoids anandamide and 2-arachidonoylglycerol are metabolised by both hydrolytic enzymes (primarily fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL)) and oxygenating enzymes (e.g. cyclooxygenase-2, COX-2). In the present article, the in vivo data for compounds inhibiting endocannabinoid metabolism have been reviewed, focussing on inflammation and pain. Potential reasons for the failure of an FAAH inhibitor in a clinical trial in patients with osteoarthritic pain are discussed. It is concluded that there is a continued potential for compounds inhibiting endocannabinoid metabolism in terms of drug development, but that it is wise not to be unrealistic in terms of expectations of success.

Keywords

2-Arachidonoylglycerol Anandamide Cyclooxygenase-2 Drug development Fatty acid amide hydrolase Monoacylglycerol lipase Pain 

Abbreviations

Δ9-THC

Δ9-Tetrahydrocannabinol

2-AG

2-Arachidonoylglycerol

AA-5-HT

N-Arachidonoyl-serotonin

AEA

Arachidonoyl ethanolamide, anandamide

(e)CB

(Endo)cannabinoid

FAAH

Fatty acid amide hydrolase

FABP5

Fatty acid binding protein 5

[35S]GTPγS

Guanosine 5′-O-(3-[35S]thio)triphosphate

IL-1ß

Interleukin-1ß

MAG

Monoacylglycerol

MGL

Monoacylglycerol lipase

NAAA

N-Acylethanolamine-hydrolyzing acid amidase

NAE

N-Acylethanolamine

NSAID

Nonsteroidal anti-inflammatory drug

PEA

Palmitoylethanolamide

OEA

Oleoylethanolamide

TRPV1

Transient receptor potential (vanilloid) 1 ion channels

Notes

Acknowledgements

The author thanks the Swedish Science Council (Grant no. 12158, medicine) and the Research Funds of the Medical Faculty, Umeå University, for their financial support of his research.

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Pharmacology and Clinical NeuroscienceUmeå UniversityUmeåSweden

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