Inhibitors of Fatty Acid Amide Hydrolase

  • Dale L. Boger
Conference paper


High pressure liquid chromatography (HPLC) fractionation of the cerebrospinal fluid (CSF) from sleep-deprived cats led to the detection of a substance that accumulated under conditions of sleep deprivation [1]. FABHRMS provided a best-fit molecular formula of C18H35NO and MS2/MS3revealed a lipid fragmentation pattern. Given the simplicity of the molecule, candidate lipid structures incorporating the molecular formula and correct degree of unsaturation were prepared and correlated with the endogenous substance (Fig. 1) [2]. Oleamide (1) proved identical with the authentic material and, with a recognition of its characteristics and solubility properties, sufficient amounts (300–400 μg) of the endogenous lipid were isolated from the CSF to permit an unambiguous correlation [2, 3]. Oleamide was shown to induce physiological sleep in rats, mice, and cats in a dose-dependent manner [3]. As in physiological sleep, the sleeping animals maintained the ability to respond to sound with an orienting reflex and attention directed toward the source. The examination of a number of close structural analogues revealed that this effect is specific for oleamide. These studies identified oleamide as an endogenous signaling fatty acid amide and provided the second prototypical member of a new and growing class of signaling molecules: fatty acid amides [4, 5].


High Pressure Liquid Chromatography Fatty Acid Amide Hydrolase Spinal Nerve Ligation Oxyanion Hole Serine Hydrolase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We gratefully acknowledge the financial support of the National Institutes of Health (DA015648), and the efforts of our long-time collaborators (R.A. Lerner, B.F. Cravatt, S.J. Henriksen, N.B. Gilula, G. Siuzdak, A.H. Lichtman, E.J. Bilsky, and R.C. Stevens).


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Copyright information

© Springer 2012

Authors and Affiliations

  1. 1.Department of ChemistryThe Scripps Research InstituteLa JollaUSA

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