Correlating FAAH and anandamide cellular uptake inhibition using N-alkylcarbamate inhibitors: From ultrapotent to hyperpotent

Biochemical Pharmacology

Volumn 92, Issue 4, 2014, Pages 669-689

  Nicolussi, Simon ^a   Chicca, Andrea ^a   Rau, Mark ^a   Rihs, Sabine ^a   Soeberdt, Michael ^b   Abels, Christoph ^b   Gertsch, Jürg ^a  

^a UNIVERSITY OF BERN   (Switzerland)

^b Dr August Wolff GmbH and Co KG Arzneimittel   (Germany)

Author keywords

Anandamide transport; Anandamide uptake inhibition; Carbamate; Correlation; FAAH inhibition

Indexed keywords

(ETHYL 5 [(DODECA 2,4 DIEN 1 YL(METHYL)CARBAMOYL]OXY]METHYL) 1,2 OXAZOLE 3 CARBOXYLIC ACID; 2 (PYRIDIN 3 YL)ETHYL [7 PHENYLHEPTA 2,4 DIEN 1 YL]CARBAMIC ACID; 2 CYANOETHYL [7 PHENYLHEPTA 2,4 DIEN 1 YL]CARBAMIC ACID; 2 PYRIDIN 2 YLMETHYL [7 PHENYLHEPTA 2,4 DIEN 1 YL]CARBAMIC ACID; 3 (1,2,3 DIHYDROTHIAZOL 2 YL)PHENYL CARBAMIC ACID; 3 (1,2,3 THIADIAZOL 4 YL)PHENYL DODECYLCARBAMIC ACID; 3 (1,2,3 THIADIAZOL 4 YL)PHENYL [7 PHENYLOCTA 2,4 DIEN 1 YL]CARBAMIC ACID; 3 (4,5 DIHYDROTHIAZOL 2 YL)PHENYL CARBAMIC ACID; 4 (4,5 DIHYDRO 1,3 THIAZOL 2 YL)PHENYL ) 7 PHENYLOCTA 2,4 DIEN 1 YL]CARBAMIC ACID; ACYLGLYCEROL LIPASE; ALBUMIN; ANANDAMIDE; CANNABINOID RECEPTOR; CARBAMIC ACID DERIVATIVE; ENDOCANNABINOID; ETHYL 5 [7 PHENYLHEPTA 2,4 DIEN 1 YL[(METHYL)CARBAMOYL)OXY]METHYL] 1,2 OXAZOLE 3 CARBOXYLIC ACID; ETHYL 5 [[[(7-PHENYLHEPTA 2,4 DIEN 1 YL)CARBAMOYL]OXY]METHYL] 1,2 OXAZOLE 3 CARBOXYLIC ACID; ETHYL 5 [[[(DODECA 2,4 DIEN 1 YLCARBAMOYL]OXY]METHYL] 1,2 OXAZOLE 3 CARBOXYLIC ACID; FATTY ACID AMIDASE; FATTY ACID AMIDASE INHIBITOR; METHYL 3 METHYL 4 [(METHYL 7 PHENYLHEPTA 2,4DIEN 1 YL]CARBAMOYL)OXY]BENZOIC ACID; NATURAL PRODUCT; PYRIDIN 3 YLMETHYL [7 PHENYLHEPTA 2,4 DIEN 1 YL]CARBAMIC ACID; PYRIDIN 4 YLMETHYL [6 (PENTYLOXY)HEXA 2,4 DIEN 1 YL]CARBAMIC ACID; PYRIDIN 4 YLMETHYL [7 PHENYLHEPTA 2,4 DIEN 1 YL]CARBAMIC ACID; SCAFFOLD PROTEIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; WOBE 490; WOBE 491; WOBE 492; AMIDASE; AMIDE; ARACHIDONIC ACID DERIVATIVE; FATTY-ACID AMIDE HYDROLASE;

ARTICLE; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG ACCUMULATION; DRUG POTENCY; DRUG UPTAKE; ENZYME INHIBITION; HUMAN; IC50; PROTEIN EXPRESSION; U937 CELL LINE; ELECTROSPRAY MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STRUCTURE ACTIVITY RELATION; TUMOR CELL LINE;

AMIDOHYDROLASES; ARACHIDONIC ACIDS; CARBAMATES; CELL LINE, TUMOR; ENDOCANNABINOIDS; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; POLYUNSATURATED ALKAMIDES; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84912074383     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2014.09.020     Document Type: Article

References (83)

1. Muccioli GG. Endocannabinoid biosynthesis and inactivation, from simple to complex. Drug Discov Today 2010;15:474-83.
2. Liu J, Wang L, Harvey-White J, Osei-Hyiaman D, Razdan R, Gong Q, et al. A biosynthetic pathway for anandamide. Proc Natl Acad Sci USA 2006;103:13345-50.
3. Liu J, Wang L, Harvey-White J, Huang B, Kim H-Y, Luquet S, et al. Multiple pathways involved in the biosynthesis of anandamide. Neuropharmacology 2008;54:1-7.
4. Placzek EA, Okamoto Y, Ueda N, Barker EL. Mechanisms for recycling and biosynthesis of endogenous cannabinoids anandamide and 2-arachidonylglycerol. J Neurochem 2008;107:987-1000.
5. Di Marzo V, Fontana A, Cadas H, Schinelli S, Cimino G, Schwartz J, et al. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 1994;372:686-91.
6. Pertwee RG, Howlett AC, Abood ME, Alexander SPH, Di Marzo V, Elphick MR, et al. International union of basic and clinical pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev 2010;62:588-631.
7. Kaczocha M, Hermann A, Glaser ST, Bojesen IN, Deutsch DG. Anandamide uptake is consistent with rate-limited diffusion and is regulated by the degree of its hydrolysis by fatty acid amide hydrolase. J Biol Chem 2006;281:9066-75.
8. Deutsch DG, Glaser ST, Howell JM, Kunz JS, Puffenbarger R, Hillard CJ, et al. The cellular uptake of anandamide is coupled to its breakdown by fatty-acid amide hydrolase. J Biol Chem 2001;276:6967-73.
9. Day T, Rakhshan F, Deutsch DG, Barker EL. Role of fatty acid amide hydrolase in the transport of the endogenous cannabinoid anandamide. Mol Pharmacol 2001;59:1369-75.
10. Oddi S, Bari M, Battista N, Barsacchi D, Cozzani I, Maccarrone M. Confocal microscopy and biochemical analysis reveal spatial and functional separation between anandamide uptake and hydrolysis in human keratinocytes. Cell Mol Life Sci 2005;62:386-95.
11. Fowler CJ, Tiger G, Ligresti A, López-Rodríguez ML, Di Marzo V. Selective inhibition of anandamide cellular uptake versus enzymatic hydrolysis - a difficult issue to handle. Eur J Pharmacol 2004;492:1-11.
12. Cravatt B, Giang D, Mayfield S. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 1996;384:83-7.
13. Ahn K, McKinney MK, Cravatt BF. Enzymatic pathways that regulate endocannabinoid signaling in the nervous system. Chem Rev 2008;108:1687-707.
14. Yu M, Ives D, Ramesha CS. Synthesis of prostaglandin E2 ethanolamide from anandamide by cyclooxygenase-2. J Biol Chem 1997;272:21181-86.
15. Kozak KR, Crews BC, Morrow JD, Wang L, Ma YH, Weinander R, et al. Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem 2002;277:44877-85.
16. Rouzer CA, Marnett LJ. Endocannabinoid oxygenation by cyclooxygenases. Lipoxygenases, and cytochromes P450: cross-talk between the eicosanoid and endocannabinoid signaling pathways. Chem Rev 2011;111:5899-921.
17. Snider NT, Walker VJ, Hollenberg PF. Oxidation of the endogenous cannabinoid arachidonoyl ethanolamide by the cytochrome P450 monooxygenases: physiological and pharmacological implications. Pharmacol Rev 2010;62:136-54.
18. Khairy H, Houssen WE. Inactivation of anandamide signaling: a continuing debate. Pharmaceuticals 2010;3:3355-70.
19. Fowler CJ. Transport of endocannabinoids across the plasma membrane and within the cell. FEBS J 2013;280:1895-904.
20. Glaser ST, Kaczocha M, Deutsch DG. Anandamide transport: a critical review. Life Sci 2005;77:1584-604.
21. Ligresti A, Morera E, Van Der Stelt M, Monory K, Lutz B, Ortar G, et al. Further evidence for the existence of a specific process for the membrane transport of anandamide. Biochem J 2004;380:265-72.
22. Chicca A, Marazzi J, Nicolussi S, Gertsch J. Evidence for bidirectional endocannabinoid transport across cell membranes. J Biol Chem 2012;287:34660-82.
23. Glaser ST, Abumrad NA, Fatade F, Kaczocha M, Studholme KM, Deutsch DG. Evidence against the presence of an anandamide transporter. Proc Natl Acad Sci USA 2003;100:4269-74.
24. Ortega-Gutiérrez S, Hawkins EG, Viso A, López-Rodríguez ML, Cravatt BF. Comparison of anandamide transport in FAAH wild-type and knockout neurons: evidence for contributions by both FAAH and the CB1 receptor to anandamide uptake. Biochemistry 2004;43:8184-90.
25. Oddi S, Fezza F, Pasquariello N, De Simone C, Rapino C, Dainese E, et al. Evidence for the intracellular accumulation of anandamide in adiposomes. Cell Mol Life Sci 2008;65:840-50.
26. Maccarrone M, Dainese E, Oddi S. Intracellular trafficking of anandamide: new concepts for signaling. Trends Biochem Sci 2010;35:601-8.
27. Oddi S, Fezza F, Pasquariello N, D'Agostino A, Catanzaro G, De Simone C, et al. Molecular identification of albumin and Hsp70 as cytosolic anandamide-binding proteins. Chem Biol 2009;16:624-32.
28. Fu J, Bottegoni G, Sasso O, Bertorelli R, Rocchia W, Masetti M, et al. A catalytically silent FAAH-1 variant drives anandamide transport in neurons. Nat Neurosci 2011;15:64-9.
29. Sanson B, Wang T, Sun J, Wang L, Kaczocha M, Ojima I, et al. Crystallographic study of FABP5 as an intracellular endocannabinoid transporter. Acta Crystallogr D Biol Crystallogr 2014;70:290-8.
30. Kaczocha M, Glaser ST, Deutsch DG. Identification of intracellular carriers for the endocannabinoid anandamide. Proc Natl Acad Sci USA 2009;106:6375-80.
31. Liedhegner ES, Vogt CD, Sem DS, Cunningham CW, Hillard CJ. Sterol carrier protein-2: binding protein for endocannabinoids. Mol Neurobiol 2014;50:149-58.
32. Ligresti A, De Petrocellis L, Hernán Pérez de la Ossa D, Aberturas R, Cristino L, Moriello AS, et al. Exploiting nanotechnologies and TRPV1 channels to investigate the putative anandamide membrane transporter. PLoS One 2010;5:e10239.
33. Di Marzo V, Ligresti A, Morera E, Nalli M, Ortar G. The anandamide membrane transporter. Structure-activity relationships of anandamide and oleoylethanolamine analogs with phenyl rings in the polar head group region. Bioorg Med Chem 2004;12:5161-9.
34. Nicolussi S, Viveros-Paredes JM, Gachet MS, Rau M, Flores-Soto ME, Blunder M, et al. Guineensine is a novel inhibitor of endocannabinoid uptake showing cannabimimetic behavioral effects in BALB/c mice. Pharmacol Res 2014;80C:52-65.
35. Hajdu Z, Nicolussi S, Rau M. Identification of endocannabinoid system-modulating N-alkylamides from heliopsis helianthoides var. scabra and Lepidium meyenii. J Nat Prod 2014;77(7):1663-9.
36. Hillard CJ, Edgemond WS, Jarrahian A, Campbell WB. Accumulation of N-arachidonoylethanolamine (anandamide) into cerebellar granule cells occurs via facilitated diffusion. J Neurochem 1997;69:631-8.
37. Beltramo M, Stella N, Calignano A, Lin SY, Makriyannis A, Piomelli D. Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 1997;277:1094-7.
38. Fegley D, Kathuria S, Mercier R, Li C, Goutopoulos A, Makriyannis A, et al. Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172. Proc Natl Acad Sci USA 2004;101:8756-61.
39. McFarland MJ, Barker EL. Anandamide transport. Pharmacol Ther 2004;104:117-35.
40. Moore SA, Nomikos GG, Dickason-Chesterfield AK, Schober DA, Schaus JM, Ying BP, et al. Identification of a high-affinity binding site involved in the transport of endocannabinoids. Proc Natl Acad Sci USA 2005;102:17852-57.
41. Di S, Boudaba C, Popescu IR, Weng F-J, Harris C, Marcheselli VL, et al. Activity-dependent release and actions of endocannabinoids in the rat hypothalamic supraoptic nucleus. J Physiol 2005;569:751-60.
42. Piomelli D, Beltramo M, Glasnapp S, Lin SY, Goutopoulos A, Xie XQ, et al. Structural determinants for recognition and translocation by the anandamide transporter. Proc Natl Acad Sci USA 1999;96:5802-7.
43. 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;128:9699-704.
44. Vandevoorde S, Fowler CJ. Inhibition of fatty acid amide hydrolase and monoacylglycerol lipase by the anandamide uptake inhibitor VDM11: evidence that VDM11 acts as an FAAH substrate. Br J Pharmacol 2005;145:885-93.
45. Hillard CJ, Shi L, Tuniki VR, Falck JR, Campbell WB. Studies of anandamide accumulation inhibitors in cerebellar granule neurons: comparison to inhibition of fatty acid amide hydrolase. J Mol Neurosci 2007;33:18-24.
46. Kaczocha M, Vivieca S, Sun J, Glaser ST, Deutsch DG. Fatty acid-binding proteins transport N-acylethanolamines to nuclear receptors and are targets of endocannabinoid transport inhibitors. J Biol Chem 2012;287:3415-24.
47. Ronesi J, Gerdeman GL, Lovinger DM. Disruption of endocannabinoid release and striatal long-term depression by postsynaptic blockade of endocannabinoid membrane transport. J Neurosci 2004;24:1673-9.
48. Mor M, Rivara S, Lodola A, Plazzi PV, Tarzia G, Duranti 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;47:4998-5008.
49. Saario SM, Poso A, Juvonen RO, Järvinen T, Salo-Ahen OMH. Fatty acid amide hydrolase inhibitors from virtual screening of the endocannabinoid system. J Med Chem 2006;49:4650-6.
50. Ortar G, Cascio MG, Moriello AS, Camalli M, Morera E, Nalli M, et al. Carbamoyl tetrazoles as inhibitors of endocannabinoid inactivation: a critical revisitation. Eur J Med Chem 2008;43:62-72.
51. Minkkilä A, Myllymäki MJ, Saario SM, Castillo-Melendez Ja, Koskinen AMP, Fowler CJ, et al. The synthesis and biological evaluation of para-substituted phenolic N-alkyl carbamates as endocannabinoid hydrolyzing enzyme inhibitors. Eur J Med Chem 2009;44:2994-3008.
52. Terwege T, Dahlhaus H, Hanekamp W, Lehr M. ω-Heteroarylalkylcarbamates as inhibitors of fatty acid amide hydrolase (FAAH). Med Chem Comm 2014;5:932-6.
53. Sit SY, Conway C, Bertekap R, Xie K, Bourin C, Burris K, et al. Novel inhibitors of fatty acid amide hydrolase. Bioorg Med Chem Lett 2007;17:3287-91.
54. Raduner S, Majewska A, Chen J, Xie X, Hamon J, Faller B, et al. Alkylamides from Echinacea are a new class of cannabinomimetics. Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects. J Biol Chem 2006;281:14192-206.
55. Chicca A, Raduner S, Pellati F, Strompen T, Altmann K-H, Schoop R, et al. Synergistic immunomopharmacological effects of N-alkylamides in Echinacea purpurea herbal extracts. Int Immunopharmacol 2009;9:850-8.
56. McKinney MK, Cravatt BF. Structure and function of fatty acid amide hydrolase. Annu Rev Biochem 2005;74:411-32.
57. Pacher P, Kunos G. Modulating the endocannabinoid system in human health and disease - successes and failures. FEBS J 2013;280:1918-43.
58. Pertwee RG. Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications. Proc Nutr Soc 2014;73:96-105.
59. Schlosburg JE, Kinsey SG, Lichtman AH. Targeting fatty acid amide hydrolase (FAAH) to treat pain and inflammation. AAPS J 2009;11:39-44.
60. Piomelli D, Tarzia G, Duranti A, Tontini A, Mor M, Compton TR, et al. Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS Drug Rev 2006;12:21-38.
61. Ahn K, Johnson D, Cravatt B. Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders. Expert Opin Drug Discov 2009;4:763-84.
62. Schlosburg JE, Boger DL, Cravatt BF, Lichtman AH. Endocannabinoid modulation of scratching response in an acute allergenic model: a new prospective. Neural Ther Target Pruritus 2009;329:314-23.
63. López-Rodríguez ML, Viso A, Ortega-Gutiérrez S, Fowler CJ, Tiger G, de Lago E, et al. Design, synthesis, and biological evaluation of new inhibitors of the endocannabinoid uptake: comparison with effects on fatty acid amidohydrolase. J Med Chem 2003;46:1512-22.
64. Maccarrone M, van der Stelt M, Rossi A, Veldink G, Vliegenthart JF, Agrò A. Anandamide hydrolysis by human cells in culture and brain. J Biol Chem 1998;273:32332-39.
65. Maccarrone M, Fiorucci L, Erba F, Bari M, Finazzi-Agrò A, Ascoli F. Human mast cells take up and hydrolyze anandamide under the control of 5-lipoxygenase and do not express cannabinoid receptors. FEBS Lett 2000;468:176-80.
66. Soeberdt M, Knie U, Abels C. Novel E, E-diene compounds and their use as medicaments and cosmetics; 2012, WO2012069605A1.
67. Soeberdt M, Knie U, Abels C. Novel E, E-diene compounds and their use as medicaments and cosmetics; 2013, EP2666766A1.
68. Abouabdellah A, Chereze N, Fayol A, Saady M, Vache J, Veronique C, et al. Carbamate derivatives of alkyl-heterocycles, preparation thereof and therapeutic use thereof; 2010, WO2010055267A1.
69. Chicca A, Caprioglio D, Minassi A, Petrucci V, Appendino G, Taglialatela-Scafati O, et al. Functionalization of β-caryophyllene generates novel polypharmacology in the endocannabinoid system. ACS Chem Biol 2014;9:1499-507.
70. Blankman J, Simon G, Cravatt B. A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem Biol 2007;14:1347-56.
71. Chang JW, Cognetta AB, Niphakis MJ, Cravatt BF. Proteome-wide reactivity profiling identifies diverse carbamate chemotypes tuned for serine hydrolase inhibition. ACS Chem Biol 2013;8:1590-9.
72. 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;12:1179-87.
73. Sulsky R, Magnin DR, Huang Y, Simpkins L, Taunk P, Patel M, et al. Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP). Bioorg Med Chem Lett 2007;17:3511-5.
74. Moreno-Sanz G, Barrera B, Armirotti A, Bertozzi SM, Scarpelli R, Bandiera T, et al. Structural determinants of peripheral O-arylcarbamate FAAH inhibitors render them dual substrates for Abcb1 and Abcg2 and restrict their access to the brain. Pharmacol Res 2014;87:87-93.
75. Moreno-Sanz G, Barrera B, Guijarro A, d'Elia I, Otero JA, Alvarez AI, et al. The ABC membrane transporter ABCG2 prevents access of FAAH inhibitor URB937 to the central nervous system. Pharmacol Res 2011;64:359-63.
76. March J. Advanced organic chemistry. John Wiley & Sons; 1992. 382.
77. Larson AL, Weber EJ. Reaction mechanisms in enviromental organic chemistry. CRC Press; 1994. p. 132-5.
78. Hillard CJ, Jarrahian A. The movement of N-arachidonoylethanolamine (anandamide) across cellular membranes. Chem Phys Lipids 2000;108:123-34.
79. Jarrahian A, Manna S, Edgemond W, Campbell W, Hillard C. Structure-activity relationships among N-arachidonylethanolamine (Anandamide) head group analogues for the anandamide transporter. J Neurochem 2000;74:2597-606.
80. De Petrocellis L, Bisogno T, Davis JB, Pertwee RG, Di Marzo V. Overlap between the ligand recognition properties of the anandamide transporter and the VR1 vanilloid receptor: inhibitors of anandamide uptake with negligible capsaicin-like activity. FEBS Lett 2000;483:52-6.
81. Jouan E, Le Vee M, Denizot C, Da Violante G, Fardel O. The mitochondrial fluorescent dye rhodamine 123 is a high-affinity substrate for organic cation transporters (OCTs) 1 and 2. Fundam Clin Pharmacol 2014;28:65-77.
82. Dickason-Chesterfield AK, Kidd SR, Moore SA, Schaus JM, Liu B, Nomikos GG, et al. Pharmacological characterization of endocannabinoid transport and fatty acid amide hydrolase inhibitors. Cell Mol Neurobiol 2006;26:407-23.
83. Björklund E, Blomqvist A, Hedlin J, Persson E, Fowler CJ. Involvement of fatty acid amide hydrolase and fatty acid binding protein 5 in the uptake of anandamide by cell lines with different levels of fatty acid amide hydrolase expression: a pharmacological study. PLoS One 2014;9(7):e103479.