Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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Natural Endocannabinoid Derivatives as Templates for the Development of FAAH Inhibitors

Author(s): Enrico Dainese, Mauro Maccarrone.

Abstract:

The endogenous cannabinoids (endocannabinoids) are amides, esters and ethers of long chain polyunsaturated fatty acids. These lipids are bioactive signaling molecules that show diverse cellular and physiological effects and play various roles both in the central nervous system and in the periphery. The discovery of N-arachidonoylethanolamine (anandamide, AEA) and of the enzyme that terminates its signaling, i.e. fatty acid amide hydrolase (FAAH), have inspired pharmacological strategies to augment endocannabinoid tone and biological activity through inhibition of FAAH. Here we discuss the role of natural endocannabinoid derivatives, like the hydroxy-anandamides (OH-AEAs) generated from AEA via lipoxygenase activity, as powerful inhibitors of FAAH. We propose that these compounds, by reversibly inhibiting FAAH, may control in vivo the endocannabinoid tone. We discuss also the potential value of OH-AEAs as templates for the development of next-generation therapeutics that act at specific sites of FAAH.

Keywords: endocannabinoids, anandamide hydrolase, nervous system, lipoxygenase, inhibition, therapy

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Article Details

VOLUME: 2
ISSUE: 5
Year: 2005
Page: [372 - 376]
Pages: 5
DOI: 10.2174/1570180054405802
Price: $58