Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders

Expert Opinion on Drug Discovery

Volumn 4, Issue 7, 2009, Pages 763-784

  Ahn, Kay ^a   Johnson, Douglas S ^a   Cravatt, Benjamin F ^b  

^a PFIZER INC   (United States)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

Anandamide; Endocannabinoid; FAAH; Faah inhibitor; Fatty acid amides; Serine hydrolase

Indexed keywords

1 (2,4 DICHLOROPHENYL) 5 (4 IODOPHENYL) 4 METHYL N (1 PIPERIDYL) 1H PYRAZOLE 3 CARBOXAMIDE; 2 (METHYLAMINO) 2 OXOETHYL CARBAMATE; 5 (4 CHLORO 3 METHYLPHENYL) 1 (4 METHYLBENZYL) N (1,3,3 TRIMETHYLBICYCLO[2.2.1]HEPTAN 2 YL) 3 PYRAZOLECARBOXAMIDE; ALPHA KETOHETEROCYCLE; ANANDAMIDE; BENZOTHIAZOLE SULFONAMIDE; BISARYLIMIDAZOLE PHENYL CARBAMATE; CYCLOHEXYLCARBAMIC ACID 3' CARBAMOYLBIPHENYL 3 YL ESTER; DICLOFENAC; FATTY ACID AMIDASE INHIBITOR; INDOMETACIN; JNJ 1661010; JP 104; JP 83; KETOOXAZOLE; LY 2183240; N OLEOYLETHANOLAMINE; N PALMITOYL ETHANOLAMINE; OL 135; OLEAMIDE; PF 3845; PF 750; RIMONABANT; SA 47; TETRAHYDRONAPTHYRIDINE; THIADIAZOLYLPIPERAZINE CARBOXAMIDE; TRIAZOLOPYRIDINE CARBOXAMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; URB 524; URB 880;

ALLODYNIA; COLITIS; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG EFFICACY; DRUG MEGADOSE; DRUG STRUCTURE; ENZYME ACTIVITY; HUMAN; HYDROLYSIS; HYPERALGESIA; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; NEUROPATHIC PAIN; NONHUMAN; PAW EDEMA; PRIORITY JOURNAL; PROTEIN ENGINEERING; REVIEW; STOMACH IRRITATION; VISCERAL PAIN; X RAY CRYSTALLOGRAPHY;

EID: 67650732783     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460440903018857     Document Type: Review

References (149)

1. Di Marzo V, Bisogno T, De Petrocellis L. Endocannabinoids and related compounds: walking back and forth between plant natural products and animal physiology. Chem Biol 2007;14(7):741-756 (Pubitemid 47081420)
2. Ahn K, McKinney MK, Cravatt BF. Enzymatic pathways that regulate endocannabinoid signaling in the nervous system. Chem Rev 2008;108(5):1687-1707 (Pubitemid 351796405)
3. Fowler CJ. The cannabinoid system and its pharmacological manipulation--a review, with emphasis upon the uptake and hydrolysis of anandamide. Fundam Clin Pharmacol 2006;20(6):549-562 (Pubitemid 44760174)
4. Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006;58(3):389-462 (Pubitemid 44394908)
5. Cravatt BF, Giang DK, Mayfield SP, et al. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 1996;384(6604):83-87 (Pubitemid 26374593)
6. McKinney MK, Cravatt BF. Structure and function of fatty acid amide hydrolase. Annu Rev Biochem 2005;74:411-432 (Pubitemid 40995513)
7. Dinh TP, Freund TF, Piomelli D. A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. Chem Phys Lipids 2002;121(1-2):149-158 (Pubitemid 36044549)
8. Mackie K. Cannabinoid receptors as therapeutic targets. Annu Rev Pharmacol Toxicol 2006;46:101-122
9. Mechoulam R. Marihuana chemistry. Science 1970;168(936):1159-1166
10. Lambert DM, Vandevoorde S, Jonsson KO, Fowler CJ. The palmitoylethanolamide family: a new class of anti-inflammatory agents? Curr Med Chem 2002;9:663-674
11. Cravatt BF, Demarest K, Patricelli MP, et al. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 2001;98(16):9371-9376
12. Kathuria S, Gaetani S, Fegley D, et al. Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 2003;9(1):76-81
13. Lichtman AH, Shelton CC, Advani T, Cravatt BF. Mice lacking fatty acid amide hydrolase exhibit a cannabinoid receptor-mediated phenotypic hypoalgesia. Pain 2004;109(3):319-327 (Pubitemid 38638709)
14. Chang L, Luo L, Palmer JA, et al. Inhibition of fatty acid amide hydrolase produces analgesia by multiple mechanisms. Br J Pharmacol 2006;148(1):102-113 (Pubitemid 43675605)
15. Russo R, Loverme J, La Rana G, et al. The fatty acid amide hydrolase inhibitor URB597 (cyclohexylcarbamic acid 3′-carbamoylbiphenyl-3-yl ester) reduces neuropathic pain after oral administration in mice. J Pharmacol Exp Ther 2007;322(1):236-242 (Pubitemid 46956375)
16. Cravatt BF, Saghatelian A, Hawkins EG, et al. Functional disassociation of the central and peripheral fatty acid amide signaling systems. Proc Natl Acad Sci USA 2004;101(29):10821-10826
17. Massa F, Marsicano G, Hermann H, et al. The endogenous cannabinoid system protects against colonic inflammation. J Clin Invest 2004;113(8):1202-1209 (Pubitemid 38544105)
18. Holt S, Comelli F, Costa B, Fowler CJ. Inhibitors of fatty acid amide hydrolase reduce carrageenan-induced hind paw inflammation in pentobarbital-treated mice: comparison with indomethacin and possible involvement of cannabinoid receptors. Br J Pharmacol 2005;146(3):467-476 (Pubitemid 41486689)
19. Naidu PS, Varvel SA, Ahn K, et al. Evaluation of fatty acid amide hydrolase inhibition in murine models of emotionality. Psychopharmacology (Berl) 2007;192(1):61-70 (Pubitemid 46673891)
20. Moreira FA, Kaiser N, Monory K, Lutz B. Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid- degrading enzyme fatty acid amide hydrolase (FAAH) is mediated by CB1 receptors. Neuropharmacology 2008;54(1):141-150 (Pubitemid 350299416)
21. Gobbi G, Bambico FR, Mangieri R, et al. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proc Natl Acad Sci USA 2005;102(51):18620-18625 (Pubitemid 43011275)
22. Lichtman AH, Leung D, Shelton CC, et al. Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity. J Pharmacol Exp Ther 2004;311(2):441-448 (Pubitemid 39391527)
23. Boger DL, Sato H, Lerner AE, et al. Exceptionally potent inhibitors of fatty acid amide hydrolase: the enzyme responsible for degradation of endogenous oleamide and anandamide. Proc Natl Acad Sci USA 2000;97:5044-5049 (Pubitemid 30313668)
24. Cravatt BF, Lichtman AH. Fatty acid amide hydrolase: an emerging therapeutic target in the endocannabinoid system. Curr Opin Chem Biol 2003;7(4):469-475 (Pubitemid 36980837)
25. Lambert DM, Fowler CJ. The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications. J Med Chem 2005;48(16):5059-5087 (Pubitemid 41113892)
26. Sugiura T, Kishimoto S, Oka S, Gokoh M. Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand. Prog Lipid Res 2006;45(5):405-446 (Pubitemid 43912907)
27. Okamoto Y, Wang J, Morishita J, Ueda N. Biosynthetic pathways of the endocannabinoid anandamide. Chem Biodivers 2007;4(8):1842-1857
28. Seierstad M, Breitenbucher JG. Discovery and Development of Fatty Acid Amide Hydrolase (FAAH) Inhibitors. J Med Chem 2008;51(23):7327-7343
29. Di Marzo V. Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov 2008;7(5):438-455
30. Basavarajappa BS. Critical enzymes involved in endocannabinoid metabolism. Protein Pept Lett 2007;14(3):237-246 (Pubitemid 46376854)
31. Mileni M, Johnson DS, Wang Z, et al. Structure-guided inhibitor design for human FAAH by interspecies active site conversion. Proc Natl Acad Sci USA 2008;105(35):12820-12824
32. Ahn K, Johnson DS, Mileni M, et al. Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem Biol 2009;16(4):411-420
33. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258(5090):1946- 1949
34. Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 2003;4(11):873-884
35. Hillard CJ, Jarrahian A. Cellular accumulation of anandamide: consensus and controversy. Br J Pharmacol 2003;140(5):802-808 (Pubitemid 37464061)
36. Glaser ST, Kaczocha M, Deutsch DG. Anandamide transport: a critical review. Life Sci 2005;77(14):1584-604
37. Schmid PC, Zuzarte-Augustin ML, Schmid HH. Properties of rat liver N-acylethanolamine amidohydrolase. J Biol Chem 1985;260(26):14145-14149
38. Deutsch DG, Chin SA. Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochem Pharmacol 1993;46(5):791-796 (Pubitemid 23272758)
39. Desarnaud F, Cadas H, Piomelli D. Anandamide amidohydrolase activity in rat brain microsomes. Identification and partial characterization. J Biol Chem 1995;270(11):6030-6035
40. Ueda N, Kurahashi Y, Yamamoto S, Tokunaga T. Partial purification and characterization of the porcine brain enzyme hydrolyzing and synthesizing anandamide. J Biol Chem 1995;270(40):23823-23827
41. Hillard CJ, Wilkison DM, Edgemond WS, Campbell WB. Characterization of the kinetics and distribution of N-arachidonylethanolamine (anandamide) hydrolysis by rat brain. Biochim Biophys Acta 1995;1257(3):249-256
42. Cravatt BF, Prospero-Garcia O, Siuzdak G, et al. Chemical characterization of a family of brain lipids that induce sleep. Science 1995;268(5216):1506-1509
43. Maurelli S, Bisogno T, De Petrocellis L, et al. Two novel classes of neuroactive fatty acid amides are substrates for mouse neuroblastoma 'anandamide amidohydrolase'. FEBS Lett 1995;377(1):82-86
44. Giang DK, Cravatt BF. Molecular characterization of human and mouse fatty acid amide hydrolases. Proc Natl Acad Sci USA 1997;94(6):2238-2242 (Pubitemid 27136858)
45. Goparaju SK, Kurahashi Y, Suzuki H, et al. Anandamide amidohydrolase of porcine brain: cDNA cloning, functional expression and site-directed mutagenesis(1). Biochim Biophys Acta 1999;1441(1):77-84
46. Egertova M, Giang DK, Cravatt BF, Elphick MR. A new perspective on cannabinoid signalling: complementary localization of fatty acid amide hydrolase and the CB1 receptor in rat brain. Proc Biol Sci 1998;265(1410):2081-2085 (Pubitemid 28502544)
47. Gulyas AI, Cravatt BF, Bracey MH, et al. Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala. Eur J Neurosci 2004;20(2):441-458 (Pubitemid 38969629)
48. Chebrou H, Bigey F, Arnaud A, Galzy P. Study of the amidase signature group. Biochim Biophys Acta 1996;1298(2):285-293
49. Patricelli MP, Lashuel HA, Giang DK, et al. Comparative characterization of a wild type and transmembrane domain-deleted fatty acid amide hydrolase: identification of the transmembrane domain as a site for oligomerization. Biochemistry 1998;37(43):15177-15187
50. Kage KL, Richardson PL, Traphagen L, et al. A high throughput fluorescent assay for measuring the activity of fatty acid amide hydrolase. J Neurosci Methods 2007;161(1):47-54 (Pubitemid 46357569)
51. Huang H, Nishi K, Tsai HJ, Hammock BD. Development of highly sensitive fluorescent assays for fatty acid amide hydrolase. Anal Biochem 2007;363(1):12-21 (Pubitemid 46348964)
52. Bracey MH, Hanson MA, Masuda KR, et al. Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling. Science 2002;298(5599):1793-1796
53. Patricelli MP, Lovato MA, Cravatt BF. Chemical and mutagenic investigations of fatty acid amide hydrolase: evidence for a family of serine hydrolases with distinct catalytic properties. Biochemistry 1999;38(31):9804- 9812 (Pubitemid 129515316)
54. Patricelli MP, Cravatt BF. Clarifying the catalytic roles of conserved residues in the amidase signature family. J Biol Chem 2000;275(25):19177-19184 (Pubitemid 30422888)
55. McKinney MK, Cravatt BF. Evidence for distinct roles in catalysis for residues of the serine-serine-lysine catalytic triad of fatty acid amide hydrolase. J Biol Chem 2003;278(39):37393-37399 (Pubitemid 37175258)
56. Patricelli MP, Cravatt BF. Fatty acid amide hydrolase competitively degrades bioactive amides and esters through a nonconventional catalytic mechanism. Biochemistry 1999;38(43):14125-14130 (Pubitemid 129520291)
57. Ahn K, Johnson DS, Fitzgerald LR, et al. Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity. Biochemistry 2007;46(45):13019-13030
58. Koutek B, Prestwich GD, Howlett AC, et al. Inhibitors of arachidonoyl ethanolamide hydrolysis. J Biol Chem 1994;269(37):22937-22940
59. Patterson JE, Ollman IR, Cravatt BF, et al. Inhibition of oleamide hydrolase catalyzed hydrolysis of the endogenous sleep-inducing lipid cis-9-octadecenamide. J Am Chem Soc 1996;118:5938-5945 (Pubitemid 26236814)
60. Boger DL, Sato H, Lerner AE, et al. Trifluoromethyl ketone inhibitors of fatty acid amide hydrolase: a probe of structural and conformational features contributing to inhibition. Bioorg Med Chem Lett 1999;9(2):265-270
61. Huang Z, Payette P, Abdullah K, et al. Functional identification of the active-site nucleophile of the human 85-kDa cytosolic phospholipase A2. Biochemistry 1996;35(12):3712-3721
62. Deutsch DG, Omeir R, Arreaza G, et al. Methyl arachidonyl fluorophosphonate: a potent irreversible inhibitor of anandamide amidase. Biochem Pharmacol 1997;53(3):255-260
63. Hoover HS, Blankman JL, Niessen S, Cravatt BF. Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling. Bioorg Med Chem Lett 2008;18(22):5838-5841
64. Leung D, Hardouin C, Boger DL, Cravatt BF. Discovering potent and selective reversible inhibitors of enzymes in complex proteomes. Nat Biotechnol 2003;21(6):687-691 (Pubitemid 36638097)
65. Kidd D, Liu Y, Cravatt BF. Profiling serine hydrolase activities in complex proteomes. Biochemistry 2001;40(13):4005-4015 (Pubitemid 32280438)
66. Liu Y, Patricelli MP, Cravatt BF. Activity-based protein profiling: the serine hydrolases. Proc Natl Acad Sci USA 1999;96(26):14694-14699 (Pubitemid 30019702)
67. Patricelli MP, Giang DK, Stamp LM, Burbaum JJ. Direct visualization of serine hydrolase activities in complex proteomes using fluorescent active site-directed probes. Proteomics 2001;1(9):1067-1071 (Pubitemid 33696471)
68. Boger DL, Miyauchi H, Du W, et al. Discovery of a potent, selective, and efficacious class of reversible alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics. J Med Chem 2005;48(6):1849-1856 (Pubitemid 40396316)
69. Romero FA, Du W, Hwang I, et al. Potent and selective alpha-ketoheterocycle-based inhibitors of the anandamide and oleamide catabolizing enzyme, fatty acid amide hydrolase. J Med Chem 2007;50(5):1058-1068 (Pubitemid 46394008)
70. Leung D, Du W, Hardouin C, et al. Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: concurrent optimization of enzyme inhibitor potency and selectivity. Bioorg Med Chem Lett 2005;15(5):1423-1428
71. Garfunkle J, Ezzili C, Rayl TJ, et al. Optimization of the central heterocycle of alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase. J Med Chem 2008;51(15):4392-4403
72. Romero FA, Hwang I, Boger DL. Delineation of a fundamental alpha-ketoheterocycle substituent effect for use in the design of enzyme inhibitors. J Am Chem Soc 2006;128(43):14004-14005 (Pubitemid 44657474)
73. Hardouin C, Kelso MJ, Romero FA, et al. Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase. J Med Chem 2007;50(14):3359-3368 (Pubitemid 47065985)
74. Kimball FS, Romero FA, Ezzili C, et al. Optimization of alpha-ketooxazole inhibitors of fatty acid amide hydrolase. J Med Chem 2008;51(4):937-947 (Pubitemid 351304701)
75. Timmons A, Seierstad M, Apodaca R, et al. Novel ketooxazole based inhibitors of fatty acid amide hydrolase (FAAH). Bioorg Med Chem Lett 2008;18(6):2109-2113
76. Fegley D, Gaetani S, Duranti A, et al. Characterization of the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3′-carbamoyl-biphenyl- 3-yl ester (URB597): effects on anandamide and oleoylethanolamide deactivation. J Pharmacol Exp Ther 2005;313(1):352-358 (Pubitemid 40411361)
77. Swinney DC. Biochemical mechanisms of drug action: what does it take for success? Nat Rev Drug Discov 2004;3(9):801-808
78. Tarzia G, Duranti A, Tontini A, et al. Design, synthesis, and structure-activity relationships of alkylcarbamic acid aryl esters, a new class of fatty acid amide hydrolase inhibitors. J Med Chem 2003;46(12):2352-2360 (Pubitemid 36637920)
79. Mor M, Rivara S, Lodola A, et al. Cyclohexylcarbamic acid 3′- or 4′-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: synthesis, quantitative structure-activity relationships, and molecular modeling studies. J Med Chem 2004;47(21):4998-5008 (Pubitemid 39314898)
80. Piomelli D, Tarzia G, Duranti A, et al. Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS Drug Rev 2006 Spring;12(1):21-38
81. Mor M, Lodola A, Rivara S, et al. Synthesis and quantitative structure-activity relationship of fatty acid amide hydrolase inhibitors: modulation at the N-portion of biphenyl-3-yl alkylcarbamates. J Med Chem 2008;51(12):3487-3498 (Pubitemid 351875005)
82. Alexander JP, Cravatt BF. Mechanism of carbamate inactivation of FAAH: implications for the design of covalent inhibitors and in vivo functional probes for enzymes. Chem Biol 2005;12(11):1179-1187 (Pubitemid 41628253)
83. Lodola A, Mor M, Rivara S, et al. Identification of productive inhibitor binding orientation in fatty acid amide hydrolase (FAAH) by QM/MM mechanistic modelling. Chem Commun (Camb) 2008;14(2):214-216 (Pubitemid 350294105)
84. AAbouabdellah A, Burnier P, Hoornaert C, et al. US20060089344;2006
85. Abouabdellah A, Almario Garcia A, Hoornaert C, et al. WO2005090347;2005
86. Zhang D, Saraf A, Kolasa T, et al. Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets. Neuropharmacology 2007;52(4):1095-1105 (Pubitemid 46319201)
87. Sit SY, Conway C, Bertekap R, et al. Novel inhibitors of fatty acid amide hydrolase. Bioorg Med Chem Lett 2007;17(12):3287-3291 (Pubitemid 46830893)
88. Ishii T, Sugane T, Maeda J, et al. WO2006088075;2006
89. Matsumoto T, Kori M, Miyazaki J, et al. WO2006054652;2006
90. Apodaca R, Breitenbucher JG, Pattabiraman K, et al. WO2006074025;2006
91. Apodaca R, Breitenbucher JG, Pattabiraman K, et al. WO2007005510;2007
92. Keith JM, Apodaca R, Xiao W, et al. Thiadiazolopiperazinyl ureas as inhibitors of fatty acid amide hydrolase. Bioorg Med Chem Lett 2008;18(17):4838-4843
93. Fay LK, Johnson DS, Lazerwith SE, et al. WO2008047229;2008
94. Ishii T, Sugane T, Kakefuda A, et al. WO2008023720;2008
95. Copeland RA. Evaluation of enzyme inhibitors in drug discovery. A guide for medicinal chemists and pharmacologists. Methods Biochem Anal 2005;46:1-265
96. Wei BQ, Mikkelsen TS, McKinney MK, et al. A second fatty acid amide hydrolase with variable distribution among placental mammals. J Biol Chem 2006;281(48):36569-36578 (Pubitemid 46049797)
97. Karbarz MJ, Luo L, Chang L, et al. 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 2009;108(1):316-329
98. Apodaca R, Breitenbucher JG, Hawryluk NA, etal. WO2008153752;2008
99. Moore SA, Nomikos GG, Dickason-Chesterfield AK, et al. Identification of a high-affinity binding site involved in the transport of endocannabinoids. Proc Natl Acad Sci USA 2005;102(49):17852-17857
100. Alexander JP, Cravatt BF. The putative endocannabinoid transport blocker LY2183240 is a potent inhibitor of FAAH and several other brain serine hydrolases. J Am Chem Soc 2006;128(30):9699-704
101. Even L, Hoornaert C. WO2008145839;2008
102. Adams J, Behnke ML, Castro AC, et al. WO2008063300;2008
103. Minkkila A, Saario SM, Kasnanen H, et al. Discovery of boronic acids as novel and potent inhibitors of fatty acid amide hydrolase. J Med Chem 2008;51(22):7057-60
104. Dembitsky VM, Quntar AA, Srebnik M. Recent advances in the medicinal chemistry of alpha-aminoboronic acids, amine-carboxyboranes and their derivatives. Mini Rev Med Chem 2004;4(9):1001-18
105. Bartolini W, Cali BM, Chen B, et al. WO2005002525;2005
106. Wang X, Sarris K, Kage K, et al. Synthesis and evaluation of benzothiazole-based analogues as novel, potent, and selective fatty acid amide hydrolase inhibitors. J Med Chem 2009;52(1):170-80
107. Kelly MG, Kincaid J, Gowlugari S, WO2009011904;2009
108. Farrell EK, Merkler DJ. Biosynthesis, degradation and pharmacological importance of the fatty acid amides. Drug Discov Today 2008;13(13-14):558-68
109. Bambico FR, Gobbi G. The cannabinoid CB1 receptor and the endocannabinoid anandamide: possible antidepressant targets. Expert Opin Ther Targets 2008;12(11):1347-66
110. Rock EM, Limebeer CL, Mechoulam R, et al. The effect of cannabidiol and URB597 on conditioned gaping (a model of nausea) elicited by a lithium-paired context in the rat. Psychopharmacology (Berl) 2008;196(3):389-95
111. Batkai S, Pacher P, Osei-Hyiaman D, et al. Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Circulation 2004;110(14):1996-2002
112. Scherma M, Panlilio LV, Fadda P, et al. Inhibition of anandamide hydrolysis by cyclohexyl carbamic acid 3′-carbamoyl-3-yl ester (URB597) reverses abuse-related behavioral and neurochemical effects of nicotine in rats. J Pharmacol Exp Ther 2008;327(2):482-90
113. Kreitzer AC, Malenka RC. Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models. Nature 2007;445(7128):643-7
114. Palmer JA, Higuera ES, Chang L, Chaplan SR. Fatty acid amide hydrolase inhibition enhances the anti-allodynic actions of endocannabinoids in a model of acute pain adapted for the mouse. Neuroscience 2008;154(4):1554-61
115. Schlosburg JE, Boger DL, Cravatt BF, Lichtman AH. Endocannabinoid modulation of scratching response in an acute allergenic model: a new prospective neural therapeutic target for pruritus. J Pharmacol Exp Ther 2009;329(1):314-23
116. Jayamanne A, Greenwood R, Mitchell VA, et al. Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. Br J Pharmacol 2006;147(3):281-8
117. Jhaveri MD, Richardson D, Kendall DA, et al. Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain. J Neurosci 2006;26(51):13318-27
118. Wise LE, Cannavacciulo R, Cravatt BF, et al. Evaluation of fatty acid amides in the carrageenan-induced paw edema model. Neuropharmacology 2008;54(1):181-8
119. Haller VL, Cichewicz DL, Welch SP. Non-cannabinoid CB1, non-cannabinoid CB2 antinociceptive effects of several novel compounds in the PPQ stretch test in mice. Eur J Pharmacol 2006;546(1-3):60-8
120. Naidu PS, Booker L, Cravatt BF, Lichtman AH. Synergy between enzyme inhibitors of fatty acid amide hydrolase and cyclooxygenase in visceral nociception. J Pharmacol Exp Ther 2009;329(1):48-56
121. Hohmann AG, Suplita RL, Bolton NM, et al. An endocannabinoid mechanism for stress-induced analgesia. Nature 2005;435(7045):1108-12
122. Storr MA, Keenan CM, Emmerdinger D, et al. Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB1 and CB2 receptors. J Mol Med 2008;86(8):925-36
123. Storr MA, Yuce B, Andrews CN, Sharkey KA. The role of the endocannabinoid system in the pathophysiology and treatment of irritable bowel syndrome. Neurogastroenterol Motil 2008;20(8):857-68
124. Patel S, Hillard CJ. Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. J Pharmacol Exp Ther 2006;318(1):304-11
125. Scherma M, Medalie J, Fratta W, et al. The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition. Neuropharmacology 2008;54(1):129-40
126. Bortolato M, Mangieri RA, Fu J, et al. Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597 in a rat model of chronic mild stress. Biol Psychiatry 2007;62(10):1103-10
127. Haller J, Barna I, Barsvari B, et al. Interactions between environmental aversiveness and the anxiolytic effects of enhanced cannabinoid signaling by FAAH inhibition in rats. Psychopharmacology (Berl) 2009, in press
128. Moise AM, Eisenstein SA, Astarita G, et al. An endocannabinoid signaling system modulates anxiety-like behavior in male Syrian hamsters. Psychopharmacology (Berl) 2008;200(3):333-46
129. Trezza V, Vanderschuren LJ. Cannabinoid and opioid modulation of social play behavior in adolescent rats: differential behavioral mechanisms. Eur Neuropsychopharmacol 2008;18(7):519-30
130. Trezza V, Vanderschuren LJ. Bidirectional cannabinoid modulation of social behavior in adolescent rats. Psychopharmacology (Berl) 2008;197(2):217-27
131. Lisboa SF, Resstel LB, Aguiar DC, Guimaraes FS. Activation of cannabinoid CB1 receptors in the dorsolateral periaqueductal gray induces anxiolytic effects in rats submitted to the Vogel conflict test. Eur J Pharmacol 2008;593(1-3):73-8
132. Batkai S, Mukhopadhyay P, Harvey-White J, et al. Endocannabinoids acting at CB1 receptors mediate the cardiac contractile dysfunction in vivo in cirrhotic rats. Am J Physiol Heart Circ Physiol 2007;293(3):H1689-95
133. Melis M, Pillolla G, Luchicchi A, et al. Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors. J Neurosci 2008;28(51):13985-94
134. Nucci C, Gasperi V, Tartaglione R, et al. Involvement of the endocannabinoid system in retinal damage after high intraocular pressure-induced ischemia in rats. Invest Ophthalmol Vis Sci 2007;48(7):2997-3004
135. Long JZ, Li W, Booker L, et al. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol 2009;5(1):37-44
136. Jessani N, Cravatt BF. The development and application of methods for activity-based protein profiling. Curr Opin Chem Biol 2004;8(1):54-9
137. Speers AE, Cravatt BF. Chemical strategies for activity-based proteomics. Chembiochem 2004;5(1):41-7
138. Sipe JC, Chiang K, Gerber AL, et al. A missense mutation in human fatty acid amide hydrolase associated with problem drug use. Proc Natl Acad Sci USA 2002;99(12):8394-9
139. Tyndale RF, Payne JI, Gerber AL, Sipe JC. The fatty acid amide hydrolase C385A (P129T) missense variant in cannabis users: studies of drug use and dependence in Caucasians. Am J Med Genet B Neuropsychiatr Genet 2007;144(5):660-6
140. Sipe JC, Waalen J, Gerber A, Beutler E. Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH). Int J Obes (Lond) 2005;29(7):755-9
141. Justinova Z, Mangieri RA, Bortolato M, et al. Fatty acid amide hydrolase inhibition heightens anandamide signaling without producing reinforcing effects in primates. Biol Psychiatry 2008;64(11):930-7
142. Jensen DP, Andreasen CH, Andersen MK, et al. The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites. J Mol Med 2007;85(5):445-9
143. Vinod KY, Sanguino E, Yalamanchili R, et al. Manipulation of fatty acid amide hydrolase functional activity alters sensitivity and dependence to ethanol. J Neurochem 2008;104(1):233-43
144. Blednov YA, Cravatt BF, Boehm SL 2nd, et al. Role of endocannabinoids in alcohol consumption and intoxication: studies of mice lacking fatty acid amide hydrolase. Neuropsychopharmacology 2007;32(7):1570-82
145. Maccarrone M, Valensise H, Bari M, et al. Relation between decreased anandamide hydrolase concentrations in human lymphocytes and miscarriage. Lancet 2000;355(9212):1326-9
146. Maccarrone M, Bisogno T, Valensise H, et al. Low fatty acid amide hydrolase and high anandamide levels are associated with failure to achieve an ongoing pregnancy after IVF and embryo transfer. Mol Hum Reprod 2002;8(2):188-95
147. Wang H, Xie H, Guo Y, et al. Fatty acid amide hydrolase deficiency limits early pregnancy events. J Clin Invest 2006;116(8):2122-31
148. Sun X, Wang H, Okabe M, et al. Genetic loss of Faah compromises male fertility in mice. Biol Reprod 2009;80(2):235-42
149. Available from: www.clinicaltrials.gov