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Inhibitory effect of macamides: N ‐benzylpalmitamide and N ‐(3‐methoxybenzyl)palmitamide on fatty acid amide hydrolase (FAAH)
Author(s) -
Alamoudi Mariam,
Bohlke Mark,
Maher Timothy,
PinoFigueroa Alejandro
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.770.8
Subject(s) - fatty acid amide hydrolase , chemistry , anandamide , enzyme , endocannabinoid system , inhibitory postsynaptic potential , biochemistry , stereochemistry , pharmacology , biology , receptor , antagonist , cannabinoid receptor , neuroscience
Lepidium meyenii (Maca), a Peruvian plant, has been used as a folk medicine for centuries. Recent studies have indicated that Maca extracts and their active constituents, macamides, act as inhibitors of fatty acid amide hydrolase (FAAH). FAAH is the enzyme responsible for the degradation of endocannabinoids. The aim of this study was to demonstrate and characterize the FAAH inhibitory effect of the macamide, N‐benzylpalmitamide, and its natural analog, N‐(3‐methoxybenzyl)palmitamide. Each compound was tested at concentrations from 1 to 100 µM, using an FAAH inhibitory activity assay, which is a fluorescence‐based method. The results demonstrated that each of the test compounds causes a concentration‐dependent inhibition of FAAH. The pre‐incubation study revealed that N‐benzylpalmitamide and N‐(3‐methoxybenzyl)palmitamide inhibit FAAH in a time‐dependent manner. The % inhibition of FAAH produced by 100 μM N‐(3‐methoxybenzyl)palmitamide without pre‐incubation was comparable to that of N‐benzylpalmitamide. However, a 120 min pre‐incubation of inhibitor with FAAH caused a significant increase in the % inhibition produced by 100 µM N‐(3‐methoxybenzyl)palmitamide. The enzyme kinetics study indicated that N‐(3‐methoxybenzyl)palmitamide is likely an uncompetitive inhibitor of FAAH. LC‐MS/MS analysis determined that N‐(3‐methoxybenzyl)palmitamide is a substrate of FAAH since it undergoes hydrolysis by FAAH. The results of this study indicated that N‐(3‐methoxybenzyl)palmitamide is a promising inhibitor of FAAH and could potentially offer a good alternative for the treatment of pain, inflammation and CNS degenerative disorders.