title: The macamide N-3-methoxybenzyl-linoleamide is a time-dependent fatty acid amide hydrolase (FAAH) inhibitor.
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.
authors.affiliation: Department of Pharmaceutical Sciences, MCPHS University, 179 Longwood Ave., Boston, MA, 02115, USA.
authors.forename: Haifa
authors.initials: H
authors.lastname: Almukadi
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Mark
authors.initials: M
authors.lastname: Böhlke
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Kelley
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Maher
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pino-Figueroa
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008041:Linoleic Acids / Q000737:chemistry / Q000494:pharmacology*; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D004791:Enzyme Inhibitors; D008041:Linoleic Acids; D008994:Monoacylglycerol Lipases; D000099252:Fatty Acid Amide Hydrolases; C587866:N-3-methoxybenzyllinoleamide; C420162:linoleamide