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The Macamide N-3-Methoxybenzyl-Linoleamide Is a Time-Dependent Fatty Acid Amide Hydrolase (FAAH) Inhibitor

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Abstract

The Peruvian plant Lepidium meyenii (Maca) has been shown to possess neuroprotective activity both in vitro and in vivo [1–3]. Previous studies have also demonstrated the activity of the pentane extract and its macamides, the most representative lipophilic constituents of Maca, in the endocannabinoid system as fatty acid amide hydrolase (FAAH) inhibitors. One of the most active macamides, N-3-methoxybenzyl-linoleamide [4, 5], was studied to determine its mechanism of interaction with FAAH and whether it has inhibitory activity on mono-acyl glycerol lipase (MAGL), the second enzyme responsible for endocannabinoid degradation [6]. Macamide concentrations from 1 to 100 μM were tested using FAAH and MAGL inhibitor assay methods and showed no effect on MAGL. Tests with other conditions were performed in order to characterize the inhibitory mechanism of FAAH inhibition. N-3-methoxybenzyl-linoleamide displayed significant time-dependent and dose-dependent FAAH inhibitory activity. The mechanism of inhibition was most likely irreversible or slowly reversible. These results suggest the potential application of macamides isolated from Maca as FAAH inhibitors, as they might act on the central nervous system to provide analgesic, anti-inflammatory, or neuroprotective effects, by modulating the release of neurotransmitters.

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Acknowledgments

We thank the American Association of Colleges of Pharmacy (AACP)-NIA Program-2012 for the invaluable support to the present study.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, MCPHS University, 179 Longwood Ave., Boston, MA, 02115, USA

    Haifa Almukadi, Hui Wu, Mark Böhlke, Charles J. Kelley, Timothy J. Maher & Alejandro Pino-Figueroa

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  1. Haifa Almukadi
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  2. Hui Wu
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  3. Mark Böhlke
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  4. Charles J. Kelley
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  5. Timothy J. Maher
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  6. Alejandro Pino-Figueroa
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Correspondence to Alejandro Pino-Figueroa.

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Almukadi, H., Wu, H., Böhlke, M. et al. The Macamide N-3-Methoxybenzyl-Linoleamide Is a Time-Dependent Fatty Acid Amide Hydrolase (FAAH) Inhibitor. Mol Neurobiol 48, 333–339 (2013). https://doi.org/10.1007/s12035-013-8499-2

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  • DOI: https://doi.org/10.1007/s12035-013-8499-2

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