N-acylethanolamine (NAE) is fatty acid amide that is required for the biosynthesis of bioactive lipid amide mediators of the endocannabinoid system.

Routes for N-acylethanolamine biosynthesis other than through NAPE-PLD activity have been identified [17].

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5. Chiarugi S, Margheriti F, De Lorenzi V, Martino E, Margheritis EG, Moscardini A, Marotta R, Chaves-Sanjuan A, Del Seppia C, Federighi G et al.. (2025) NAPE-PLD is target of thiazide diuretics. Cell Chem Biol, [Epub ahead of print]. [PMID:39999832]

6. Habib AM, Okorokov AL, Hill MN, Bras JT, Lee MC, Li S, Gossage SJ, van Drimmelen M, Morena M, Houlden H et al.. (2019) Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity. Br J Anaesth, 123 (2): e249-e253. DOI: 10.1016/j.bja.2019.02.019 [PMID:30929760]

7. Karbarz MJ, Luo L, Chang L, Tham CS, Palmer JA, Wilson SJ, Wennerholm ML, Brown SM, Scott BP, Apodaca RL et al.. (2009) Biochemical and biological properties of 4-(3-phenyl-[1,2,4] thiadiazol-5-yl)-piperazine-1-carboxylic acid phenylamide, a mechanism-based inhibitor of fatty acid amide hydrolase. Anesth Analg, 108 (1): 316-29. [PMID:19095868]

8. Keith JM, Apodaca R, Xiao W, Seierstad M, Pattabiraman K, Wu J, Webb M, Karbarz MJ, Brown S, Wilson S et al.. (2008) Thiadiazolopiperazinyl ureas as inhibitors of fatty acid amide hydrolase. Bioorg Med Chem Lett, 18 (17): 4838-43. [PMID:18693015]

9. Li Y, Chen Q, Yang L, Li Y, Zhang Y, Qiu Y, Ren J, Lu C. (2017) Identification of highly potent N-acylethanolamine acid amidase (NAAA) inhibitors: Optimization of the terminal phenyl moiety of oxazolidone derivatives. Eur J Med Chem, 139: 214-221. [PMID:28802121]

10. Li Y, Zhou P, Chen H, Chen Q, Kuang X, Lu C, Ren J, Qiu Y. (2018) Inflammation-restricted anti-inflammatory activities of a N-acylethanolamine acid amidase (NAAA) inhibitor F215. Pharmacol Res, 132: 7-14. [PMID:29572189]

11. Liu Q, Tonai T, Ueda N. (2002) Activation of N-acylethanolamine-releasing phospholipase D by polyamines. Chem Phys Lipids, 115 (1-2): 77-84. [PMID:12047899]

12. Mock ED, Mustafa M, Gunduz-Cinar O, Cinar R, Petrie GN, Kantae V, Di X, Ogasawara D, Varga ZV, Paloczi J et al.. (2020) Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice. Nat Chem Biol, 16 (6): 667-675. [PMID:32393901]

13. Petersen G, Hansen HS. (1999) N-acylphosphatidylethanolamine-hydrolysing phospholipase D lacks the ability to transphosphatidylate. FEBS Lett, 455 (1-2): 41-4. [PMID:10428468]

14. Ribeiro A, Pontis S, Mengatto L, Armirotti A, Chiurchiù V, Capurro V, Fiasella A, Nuzzi A, Romeo E, Moreno-Sanz G et al.. (2015) A Potent Systemically Active N-Acylethanolamine Acid Amidase Inhibitor that Suppresses Inflammation and Human Macrophage Activation. ACS Chem Biol, 10 (8): 1838-46. [PMID:25874594]

15. Solorzano C, Zhu C, Battista N, Astarita G, Lodola A, Rivara S, Mor M, Russo R, Maccarrone M, Antonietti F et al.. (2009) Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation. Proc Natl Acad Sci USA, 106 (49): 20966-71. [PMID:19926854]

16. Tsuboi K, Hilligsmann C, Vandevoorde S, Lambert DM, Ueda N. (2004) N-cyclohexanecarbonylpentadecylamine: a selective inhibitor of the acid amidase hydrolysing N-acylethanolamines, as a tool to distinguish acid amidase from fatty acid amide hydrolase. Biochem J, 379 (Pt 1): 99-106. [PMID:14686878]

17. Tsuboi K, Ikematsu N, Uyama T, Deutsch DG, Tokumura A, Ueda N. (2013) Biosynthetic pathways of bioactive N-acylethanolamines in brain. CNS Neurol Disord Drug Targets, 12 (1): 7-16. [PMID:23394527]

18. Ueda N, Yamanaka K, Yamamoto S. (2001) Purification and characterization of an acid amidase selective for N-palmitoylethanolamine, a putative endogenous anti-inflammatory substance. J Biol Chem, 276 (38): 35552-7. [PMID:11463796]

19. Watabiki T, Tsuji N, Kiso T, Ozawa T, Narazaki F, Kakimoto S. (2017) In vitro and in vivo pharmacological characterization of ASP8477: A novel highly selective fatty acid amide hydrolase inhibitor. Eur J Pharmacol, 815: 42-48. [PMID:29017758]

20. Wei BQ, Mikkelsen TS, McKinney MK, Lander ES, Cravatt BF. (2006) A second fatty acid amide hydrolase with variable distribution among placental mammals. J Biol Chem, 281 (48): 36569-78. [PMID:17015445]

Stephen P.H. Alexander Associate Professor in Molecular Pharmacology Life Sciences E Floor University of Nottingham Medical School Nottingham NG7 2UH UK Patrick Doherty Wolfson Centre for Age-Related Diseases Kings College London Wolfson Wing, Hodgkin Building Guys Campus London SE1 1UL UK Christopher J. Fowler Building 6B, 2nd floor, University Hospital of Umeå SE-90187 Umeå Sweden Jürg Gertsch Institute of Biochemistry and Molecular Medicine University of Bern Bühlstrasse 28, CH-3012 Bern Switzerland Mario van der Stelt Department of Molecular Physiology Leiden Institute of Chemistry Leiden University 2333 CC Leiden The Netherlands