The novel reversible fatty acid amide hydrolase inhibitor ST4070 increases endocannabinoid brain levels and counteracts neuropathic pain in different animal models

Journal of Pharmacology and Experimental Therapeutics

Volumn 342, Issue 1, 2012, Pages 188-195

  Caprioli, Antonio ^a   Coccurello, Roberto ^c   Rapino, Cinzia ^b   Di Serio, Stefano ^a   Di Tommaso, Monia ^b   Vertechy, Mario ^a   Vacca, Valentina ^c   Battista, Natalia ^b,d   Pavone, Flaminia ^c   Maccarrone, Mauro ^b,d   Borsini, Franco ^a  

^a Sigma Tau SpA   (Italy)

^b UNIVERSITY OF TERAMO   (Italy)

^c CNR   (Italy)

^d IRCCS FONDAZIONE SANTA LUCIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1 BIPHENYL 4 YLETHENYL PIPERIDINE 1 CARBOXYLATE; 2 [[1 METHYL 3 OXO 3 [4 (TRIFLUOROMETHYL)PHENYL] 1 PROPENYL]AMINO 3 [4 [2 (5 METHYL 2 PHENYL 4 OXAZOYL)ETHOXY]PHENYL]PROPYL]CARBAMIC ACID ETHYL ESTER; 2 ARACHIDONOYLGLYCEROL; 7 PHENYL 1 [5 (2 PYRIDINYL) 2 OXAZOLYL] 1 HEPTANONE; ANALGESIC AGENT; ANANDAMIDE; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID 2 RECEPTOR ANTAGONIST; CANNABINOID RECEPTOR ANTAGONIST; CYCLOHEXYLCARBAMIC ACID 3' CARBAMOYLBIPHENYL 3 YL ESTER; ENDOCANNABINOID; FATTY ACID AMIDASE; FATTY ACID AMIDASE INHIBITOR; PALMIDROL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PREGABALIN; ST 4070; STREPTOZOCIN; UNCLASSIFIED DRUG; VINCRISTINE;

ALLODYNIA; ANALGESIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN LEVEL; BRAIN TISSUE; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFICACY; ENZYME ACTIVITY; ENZYME INHIBITION; EXPERIMENTAL TEST; MALE; MECHANICAL STIMULATION; MOUSE; NERVE COMPRESSION; NERVE INJURY; NEUROPATHIC PAIN; NOCICEPTION; NONHUMAN; PAIN THRESHOLD; PRIORITY JOURNAL; RANDALL SELITTO TEST; RAT; STREPTOZOCIN DIABETES; VON FREY TEST;

ACUTE PAIN; AMIDOHYDROLASES; ANALGESICS; ANIMALS; ARACHIDONIC ACIDS; BRAIN; ENDOCANNABINOIDS; GLYCERIDES; MALE; MICE; MICE, INBRED NOD; NEURALGIA; POLYUNSATURATED ALKAMIDES; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84862491020     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.111.191403     Document Type: Article

References (59)

1. Ahn K, Johnson DS, and Cravatt BF (2009) Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders. Expert Opin Drug Discov 4:763-784.
2. Aloe L, Leon A, and Levi-Montalcini RL (1993) A proposed autacoid mechanism controlling mastocyte behaviour. Agents Actions 39:C145-C147. (Pubitemid 23276753)
3. Aloisi AM and Bonifazi M (2006) Sex hormones, central nervous system and pain. Horm Behav 50:1-7. (Pubitemid 43792491)
4. Ashton JC and Milligan ED (2008) Cannabinoids for the treatment of neuropathic pain: clinical evidence. Curr Opin Investig Drugs 9:65-75.
5. Backonja M and Glanzman RL (2003) Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials. Clin Ther 25:81-104. (Pubitemid 36206739)
6. Benito C, Romero JP, Tolón RM, Clemente D, Docagne F, Hillard CJ, Guaza C, and Romero J (2007) Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis. J Neurosci 27:2396-2402. (Pubitemid 46340977)
7. Bennett GJ and Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33:87-107.
8. Bisogno T, De Petrocellis L, and Di Marzo V (2002) Fatty acid amide hydrolase, an enzyme with many bioactive substrates. Possible therapeutic implications. Curr Pharm Des 8:533-547. (Pubitemid 34449864)
9. Calignano A, La Rana G, Giuffrida A, and Piomelli D (1998) Control of pain initiation by endogenous cannabinoids. Nature 394:277-281. (Pubitemid 28335039)
10. Calignano A, La Rana G, and Piomelli D (2001) Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide. Eur J Pharmacol 419:191-198. (Pubitemid 32568218)
11. Chang L, Luo L, Palmer JA, Sutton S, Wilson SJ, Barbier AJ, Breitenbucher JG, Chaplan SR, and Webb M (2006) Inhibition of fatty acid amide hydrolase produces analgesia by multiple mechanisms. Br J Pharmacol 148:102-113. (Pubitemid 43675605)
12. Collin C, Ehler E, Waberzinek G, Alsindi Z, Davies P, Powell K, Notcutt W, O'Leary C, Ratcliffe S, Nováková I, et al. (2010) A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res 32:451-459.
13. Coomber B, O'Donoghue MF, and Mason R (2008) Inhibition of endocannabinoid metabolism attenuates enhanced hippocampal neuronal activity induced by kainic acid. Synapse 62:746-755.
14. 1, TRPV1 and PPAR γ receptors and neurotrophic factors. Pain 139:541-550.
15. Costa B, Conti S, Giagnoni G, and Colleoni M (2002) Therapeutic effect of the endogenous fatty acid amide, palmitoylethanolamide, in rat acute inflammation: inhibition of nitric oxide and cyclo-oxygenase systems. Br J Pharmacol 137:413-420. (Pubitemid 35221894)
16. Cravatt BF, Demarest K, Patricelli MP, Bracey MH, Giang DK, Martin BR, and Lichtman AH (2001) Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acidamide hydrolase. Proc Natl Acad Sci U S A 98:9371-9376. (Pubitemid 32743923)
17. Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, and Gilula NB (1996) Molecular characterization of an enzyme that degrades neuromodulatory fattyacid amides. Nature 384:83-87. (Pubitemid 26374593)
18. D'Agostino G, La Rana G, Russo R, Sasso O, Iacono A, Esposito E, Mattace Raso G, Cuzzocrea S, Loverme J, Piomelli D, et al. (2009) Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-κB nuclear signalling in dorsal root ganglia. Eur J Pharmacol 613:54-59.
19. D'Agostino G, La Rana G, Russo R, Sasso O, Iacono A, Esposito E, Raso GM, Cuzzocrea S, Lo Verme J, Piomelli D, et al. (2007) Acute intracerebroventricular administration of palmitoylethanolamide, an endogenous peroxisome proliferator-activated receptor-α agonist, modulates carrageenan-induced paw edema in mice. J Pharmacol Exp Ther 322:1137-1143. (Pubitemid 47295805)
20. De Filippis D, Luongo L, Cipriano M, Palazzo E, Cinelli MP, de Novellis V, Maione S, and Iuvone T (2011) Palmitoylethanolamide reduces granuloma-induced hyperalgesia by modulation of mast cell activation in rats. Mol Pain 7:3.
21. De Petrocellis L, Davis JB, and Di Marzo V (2001) Palmitoylethanolamide enhances anandamide stimulation of human vanilloid VR1 receptors. FEBS Lett 506:253-256. (Pubitemid 32964824)
22. Desroches J, Guindon J, Lambert C, and Beaulieu P (2008) Modulation of the anti-nociceptive effects of 2-arachidonoyl glycerol by peripherally administered FAAH and MGL inhibitors in a neuropathic pain model. Br J Pharmacol 155:913-924.
23. Endocannabinoid Research Group, De Filippis D, D'Amico A, Cipriano M, Petrosino S, Orlando P, Di Marzo V, and Iuvone T (2010) Levels of endocannabinoids and palmitoylethanolamide and their pharmacological manipulation in chronic granulomatous inflammation in rats. Pharmacol Res 61:321-328.
24. Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, and Leon A (1995) Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci U S A 92:3376-3380.
25. Fezza F, De Simone C, Amadio D, and Maccarrone M (2008) Fatty acid amide hydrolase: a gate-keeper of the endocannabinoid system. Subcell Biochem 49:101-132.
26. Gattinoni S, De Simone C, Dallavalle S, Fezza F, Nannei R, Amadio D, Minetti P, Quattrociocchi G, Caprioli A, Borsini F, et al. (2010) Enol carbamates as inhibitors of fatty acid amide hydrolase (FAAH) endowed with high selectivity for FAAH over the other targets of the endocannabinoid system. Chem Med Chem 5:357-360.
27. Genovese T, Esposito E, Mazzon E, Di Paola R, Meli R, Bramanti P, Piomelli D, Calignano A, and Cuzzocrea S (2008) Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury. J Pharmacol Exp Ther 326:12-23. (Pubitemid 351872139)
28. Guasti L, Richardson D, Jhaveri M, Eldeeb K, Barrett D, Elphick MR, Alexander SP, Kendall D, Michael GJ, and Chapman V (2009) Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain. Mol Pain 5:35.
29. Högestätt ED, Jönsson BA, Ermund A, Andersson DA, Björk H, Alexander JP, Cravatt BF, Basbaum AI, and Zygmunt PM (2005) Conversion of acetaminophen to the bioactive N-acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system. J Biol Chem 280:31405-31412. (Pubitemid 41291881)
30. Jayamanne A, Greenwood R, Mitchell VA, Aslan S, Piomelli D, and Vaughan CW (2006) Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. Br J Pharmacol 147:281-288. (Pubitemid 43214685)
31. Jhaveri MD, Richardson D, Kendall DA, Barrett DA, and Chapman V (2006) Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain. J Neurosci 26:13318-13327. (Pubitemid 46011642)
32. Jhaveri MD, Richardson D, Robinson I, Garle MJ, Patel A, Sun Y, Sagar DR, Bennett AJ, Alexander SP, Kendall DA, et al. (2008) Inhibition of fatty acid amide hydrolase and cyclooxygenase-2 increases levels of endocannabinoid related molecules and produces analgesia via peroxisome proliferator-activated receptor-α in a model of inflammatory pain. Neuropharmacology 55:85-93.
33. Karanian DA, Brown QB, Makriyannis A, Kosten TA, and Bahr BA (2005) Dual modulation of endocannabinoid transport and fatty acid amide hydrolase protects against excitotoxicity. J Neurosci 25:7813-7820. (Pubitemid 41208653)
34. Karanian DA, Karim SL, Wood JT, Williams JS, Lin S, Makriyannis A, and Bahr BA (2007) Endocannabinoid enhancement protects against kainic acid-induced seizures and associated brain damage. J Pharmacol Exp Ther 322:1059-1066. (Pubitemid 47295815)
35. Kinsey SG, Long JZ, O'Neal ST, Abdullah RA, Poklis JL, Boger DL, Cravatt BF, and Lichtman AH (2009) Blockade of endocannabinoid-degrading enzymes attenuates neuropathic pain. J Pharmacol Exp Ther 330:902-910.
36. Kinsey SG, Naidu PS, Cravatt BF, Dudley DT, and Lichtman AH (2011) Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis and related thermal hyperalgesia in mice. Pharmacol Biochem Behav 99:718-725.
37. Lambert DM and Di Marzo V (1999) The palmitoylethanolamide and oleamide enigmas: are these two fatty acid amides cannabimimetic? Curr Med Chem 6:757-773. (Pubitemid 29399503)
38. Lichtman AH, Leung D, Shelton CC, Saghatelian A, Hardouin C, Boger DL, and Cravatt BF (2004b) Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity. J Pharmacol Exp Ther 311:441-448. (Pubitemid 39391527)
39. Lichtman AH, Shelton CC, Advani T, and Cravatt BF (2004a) Mice lacking fatty acid amidehydrolase exhibit a cannabinoid receptor-mediated phenotypic hypoalgesia. Pain 109:319-327. (Pubitemid 38638709)
40. Loría F, Petrosino S, Mestre L, Spagnolo A, Correa F, Hernangómez M, Guaza C, Di Marzo V, and Docagne F (2008) Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. Eur J Neurosci 28:633-641.
41. Lo Verme J, Fu J, Astarita G, La Rana G, Russo R, Calignano A, and Piomelli D (2005) The nuclear receptor peroxisome proliferator-activated receptor-α mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol 67:15-19. (Pubitemid 40069962)
42. Luvisetto S, Marinelli S, Rossetto O, Montecucco C, and Pavone F (2004) Central injection of botulinum neurotoxins: behavioural effects in mice. Behav Pharmacol 15:233-240. (Pubitemid 38859606)
43. Mallet C, Daulhac L, Bonnefont J, Ledent C, Etienne M, Chapuy E, Libert F, and Eschalier A (2008) Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. Pain 139:190-200.
44. McKinney MK and Cravatt BF (2005) Structure and function of fatty acid amide hydrolase. Annu Rev Biochem 74:411-432. (Pubitemid 40995513)
45. Naidu PS, Kinsey SG, Guo TL, Cravatt BF, and Lichtman AH (2010) Regulation of inflammatory pain by inhibition of fatty acid amide hydrolase. J Pharmacol Exp Ther 334:182-190.
46. Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, and Haines D (2007) Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain 133:210-220. (Pubitemid 350141682)
47. Palmer JA, Higuera ES, Chang L, and Chaplan SR (2008) Fatty acid amide hydrolase inhibition enhances the anti-allodynic actions of endocannabinoids in a model of acute pain adapted for the mouse. Neuroscience 154:1554-1561.
48. Patel S, Carrier EJ, Ho WS, Rademacher DJ, Cunningham S, Reddy DS, Falck JR, Cravatt BF, and Hillard CJ (2005) The postmortal accumulation of brain N-arachidonylethanolamine (anandamide) is dependent upon fatty acidamide hydrolase activity. J Lipid Res 46:342-349. (Pubitemid 40271098)
49. Petrosino S and Di Marzo V (2010) FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels. Curr Opin Investig Drugs 11:51-62.
50. Russo R, Loverme J, La Rana G, Compton TR, Parrott J, Duranti A, Tontini A, Mor M, Tarzia G, Calignano A, et al. (2007) 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 322:236-242. (Pubitemid 46956375)
51. Sagar DR, Kendall DA, and Chapman V (2008) Inhibition of fatty acid amide hydrolase produces PPAR-α-mediated analgesia in a rat model of inflammatory pain. Br J Pharmacol 155:1297-1306.
52. Schlosburg JE, Kinsey SG, and Lichtman AH (2009) Targeting fatty acid amide hydrolase (FAAH) to treat pain and inflammation. AAPS J 11:39-44.
53. Schuelert N, Johnson MP, Oskins JL, Jassal K, Chambers MG, and McDougall JJ (2011) Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces nociception in spontaneous and chemically induced models of osteoarthritis. Pain 152:975-981.
54. Simon GM and Cravatt BF (2010) Characterization of mice lacking candidate N-acyl ethanolamine biosynthetic enzymes provides evidence for multiple pathways that contribute to endocannabinoid production in vivo. Mol Biosyst 6:1411-1418.
55. Tsou K, Brown S, Sañudo-Peña MC, Mackie K, and Walker JM (1998) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83:393-411. (Pubitemid 28062631)
56. Walker JM and Hohmann AG (2005) Cannabinoid mechanisms of pain suppression. Handb Exp Pharmacol 168:509-554.
57. Wallace VC, Segerdahl AR, Lambert DM, Vandevoorde S, Blackbeard J, Pheby T, Hasnie F, and Rice AS (2007) The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy. Br J Pharmacol 151:1117-1128. (Pubitemid 47195540)
58. Zias J, Stark H, Sellgman J, Levy R, Werker E, Breuer A, Mechoulam R (1993) Early medical use of cannabis. Nature 363:215.
59. Zuo Y, Perkins NM, Tracey DJ, and Geczy CL (2003) Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain 105:467-479. (Pubitemid 37186908)