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Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase
Published on: November 23, 2016
The macamide N-3-methoxybenzyl-linoleamide is a time-dependent fatty acid amide hydrolase (FAAH) inhibitor
Haifa Almukadi1, Hui Wu, Mark Böhlke
1Department of Pharmaceutical Sciences, MCPHS University, 179 Longwood Ave., Boston, MA, 02115, USA.
Abstract:
The Peruvian plant Lepidium meyenii (Maca) has been shown to possess neuroprotective activity both in vitro and in vivo. 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, 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. 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.
Insights
Maca
Area of Science:
- Neuropharmacology
- Natural Product Chemistry
Background:
- Lepidium meyenii (Maca) exhibits neuroprotective properties.
- Maca's lipophilic constituents, macamides, inhibit fatty acid amide hydrolase (FAAH).
- Endocannabinoid system enzymes like FAAH and mono-acyl glycerol lipase (MAGL) are key targets.
Purpose of the Study:
- Investigate the mechanism of N-3-methoxybenzyl-linoleamide (a macamide) interaction with FAAH.
- Determine if N-3-methoxybenzyl-linoleamide inhibits MAGL.
Main Methods:
- Enzyme inhibition assays for FAAH and MAGL.
- Testing macamide concentrations from 1 to 100 μM.
- Characterization of FAAH inhibition kinetics.
Main Results:
- N-3-methoxybenzyl-linoleamide showed no inhibitory effect on MAGL.
- Significant time-dependent and dose-dependent inhibition of FAAH was observed.
- The FAAH inhibition mechanism appears irreversible or slowly reversible.
Conclusions:
- Macamides from Maca show potential as FAAH inhibitors.
- Modulating FAAH may offer neuroprotective, analgesic, and anti-inflammatory effects via the central nervous system.
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