30. Suplita RL, II, Farthing JN, Gutierrez T, Hohmann AG (2005) Inhibition of fatty-acid amide
hydrolase enhances cannabinoid stress-induced analgesia: sites of action in the dorsolateral
periaqueductal gray and rostral ventromedial medulla. Neuropharmacology 49(8):1201–1209.
doi:10.1016/j.neuropharm.2005.07.007 S0028-3908(05)00263-7 [pii]
31. Lichtman AH, Leung D, Shelton CC, Saghatelian A, Hardouin C, Boger DL, Cravatt BF
(2004) Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence
for an unprecedented combination of potency and selectivity. J Pharmacol Exp Ther 311
(2):441–448. doi:10.1124/jpet.104.069401 jpet.104.069401 [pii]
32. Chang L, Luo L, Palmer JA, Sutton S, Wilson SJ, Barbier AJ, Breitenbucher JG, Chaplan SR,
Webb M (2006) Inhibition of fatty acid amide hydrolase produces analgesia by multiple
mechanisms. Br J Pharmacol 148(1):102–113. doi:10.1038/sj.bjp.0706699 0706699 [pii]
33. Jayamanne A, Greenwood R, Mitchell VA, Aslan S, Piomelli D, Vaughan CW (2006) Actions
of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. Br J
Pharmacol 147(3):281–288. doi:10.1038/sj.bjp.0706510 0706510 [pii]
34. Ahn K, Johnson DS, Mileni M, Beidler D, Long JZ, McKinney MK, Weerapana E, Sadagopan
N, Liimatta M, Smith SE, Lazerwith S, Stiff C, Kamtekar S, Bhattacharya K, Zhang Y,
Swaney S, Van Becelaere K, Stevens RC, Cravatt BF (2009) Discovery and characterization
of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem Biol 16(4):411–
420. doi:10.1016/j.chembiol.2009.02.013 S1074-5521(09)00080-5 [pii]
35. Egertova M, Cravatt BF, Elphick MR (2003) Comparative analysis of fatty acid amide
hydrolase and cb(1) cannabinoid receptor expression in the mouse brain: evidence of a
widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling.
Neuroscience 119(2):481–496. doi:S0306452203001453 [pii]
36. Long JZ, LaCava M, Jin X, Cravatt BF (2011) An anatomical and temporal portrait of
physiological substrates for fatty acid amide hydrolase. J Lipid Res 52(2):337–344. doi:10.
1194/jlr.M012153 jlr.M012153 [pii]
37. Schlosburg JE, Kinsey SG, Lichtman AH (2009) Targeting fatty acid amide hydrolase (FAAH)
to treat pain and inflammation. AAPS J 11(1):39–44. doi:10.1208/s12248-008-9075-y
38. Hwang J, Adamson C, Butler D, Janero DR, Makriyannis A, Bahr BA (2010) Enhancement of
endocannabinoid signaling by fatty acid amide hydrolase inhibition: a neuroprotective
therapeutic modality. Life Sci 86(15–16):615–623. doi:10.1016/j.lfs.2009.06.003 S0024-3205
(09)00262-8 [pii]
39. Fowler CJ, Jonsson KO, Tiger G (2001) Fatty acid amide hydrolase: biochemistry,
pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2arachidonoylglycerol, palmitoylethanolamide, and oleamide. Biochem Pharmacol 62(5):517–
526. doi:S0006-2952(01)00712-2 [pii]
40. Lambert DM, Fowler CJ (2005) The endocannabinoid system: drug targets, lead compounds,
and potential therapeutic applications. J Med Chem 48(16):5059–5087. doi:10.1021/jm058183t
41. Ahn K, McKinney MK, Cravatt BF (2008) Enzymatic pathways that regulate endocannabinoid
signaling in the nervous system. Chem Rev 108(5):1687–1707. doi:10.1021/cr0782067
42. Ahn K, Johnson DS, 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(7):763–784.
doi:10.1517/17460440903018857
43. Sipe JC, Waalen J, Gerber A, Beutler E (2005) Overweight and obesity associated with a
missense polymorphism in fatty acid amide hydrolase (FAAH). Int J Obes (Lond) 29(7):755–
759. doi:10.1038/sj.ijo.0802954 0802954 [pii]
44. Sipe JC, Chiang K, Gerber AL, Beutler E, Cravatt BF (2002) A missense mutation in human
fatty acid amide hydrolase associated with problem drug use. Proc Natl Acad Sci USA 99
(12):8394–8399. doi:10.1073/pnas.082235799 99/12/8394 [pii]
45. Otrubova K, Ezzili C, Boger DL (2011) The discovery and development of inhibitors of fatty
acid amide hydrolase (FAAH). Bioorg Med Chem Lett 21(16):4674–4685. doi:10.1016/j.
bmcl.2011.06.096 S0960-894X(11)00887-0 [pii]
46. Bachovchin DA, Cravatt BF (2012) The pharmacological landscape and therapeutic potential
of serine hydrolases. Nat Rev Drug Discov 11(1):52–68. doi:10.1038/nrd3620 nrd3620 [pii]
Molecular Dynamics Analysis of FAAH Complexed with Anandamide
129
hydrolase enhances cannabinoid stress-induced analgesia: sites of action in the dorsolateral
periaqueductal gray and rostral ventromedial medulla. Neuropharmacology 49(8):1201–1209.
doi:10.1016/j.neuropharm.2005.07.007 S0028-3908(05)00263-7 [pii]
31. Lichtman AH, Leung D, Shelton CC, Saghatelian A, Hardouin C, Boger DL, Cravatt BF
(2004) Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence
for an unprecedented combination of potency and selectivity. J Pharmacol Exp Ther 311
(2):441–448. doi:10.1124/jpet.104.069401 jpet.104.069401 [pii]
32. Chang L, Luo L, Palmer JA, Sutton S, Wilson SJ, Barbier AJ, Breitenbucher JG, Chaplan SR,
Webb M (2006) Inhibition of fatty acid amide hydrolase produces analgesia by multiple
mechanisms. Br J Pharmacol 148(1):102–113. doi:10.1038/sj.bjp.0706699 0706699 [pii]
33. Jayamanne A, Greenwood R, Mitchell VA, Aslan S, Piomelli D, Vaughan CW (2006) Actions
of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. Br J
Pharmacol 147(3):281–288. doi:10.1038/sj.bjp.0706510 0706510 [pii]
34. Ahn K, Johnson DS, Mileni M, Beidler D, Long JZ, McKinney MK, Weerapana E, Sadagopan
N, Liimatta M, Smith SE, Lazerwith S, Stiff C, Kamtekar S, Bhattacharya K, Zhang Y,
Swaney S, Van Becelaere K, Stevens RC, Cravatt BF (2009) Discovery and characterization
of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem Biol 16(4):411–
420. doi:10.1016/j.chembiol.2009.02.013 S1074-5521(09)00080-5 [pii]
35. Egertova M, Cravatt BF, Elphick MR (2003) Comparative analysis of fatty acid amide
hydrolase and cb(1) cannabinoid receptor expression in the mouse brain: evidence of a
widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling.
Neuroscience 119(2):481–496. doi:S0306452203001453 [pii]
36. Long JZ, LaCava M, Jin X, Cravatt BF (2011) An anatomical and temporal portrait of
physiological substrates for fatty acid amide hydrolase. J Lipid Res 52(2):337–344. doi:10.
1194/jlr.M012153 jlr.M012153 [pii]
37. Schlosburg JE, Kinsey SG, Lichtman AH (2009) Targeting fatty acid amide hydrolase (FAAH)
to treat pain and inflammation. AAPS J 11(1):39–44. doi:10.1208/s12248-008-9075-y
38. Hwang J, Adamson C, Butler D, Janero DR, Makriyannis A, Bahr BA (2010) Enhancement of
endocannabinoid signaling by fatty acid amide hydrolase inhibition: a neuroprotective
therapeutic modality. Life Sci 86(15–16):615–623. doi:10.1016/j.lfs.2009.06.003 S0024-3205
(09)00262-8 [pii]
39. Fowler CJ, Jonsson KO, Tiger G (2001) Fatty acid amide hydrolase: biochemistry,
pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2arachidonoylglycerol, palmitoylethanolamide, and oleamide. Biochem Pharmacol 62(5):517–
526. doi:S0006-2952(01)00712-2 [pii]
40. Lambert DM, Fowler CJ (2005) The endocannabinoid system: drug targets, lead compounds,
and potential therapeutic applications. J Med Chem 48(16):5059–5087. doi:10.1021/jm058183t
41. Ahn K, McKinney MK, Cravatt BF (2008) Enzymatic pathways that regulate endocannabinoid
signaling in the nervous system. Chem Rev 108(5):1687–1707. doi:10.1021/cr0782067
42. Ahn K, Johnson DS, 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(7):763–784.
doi:10.1517/17460440903018857
43. Sipe JC, Waalen J, Gerber A, Beutler E (2005) Overweight and obesity associated with a
missense polymorphism in fatty acid amide hydrolase (FAAH). Int J Obes (Lond) 29(7):755–
759. doi:10.1038/sj.ijo.0802954 0802954 [pii]
44. Sipe JC, Chiang K, Gerber AL, Beutler E, Cravatt BF (2002) A missense mutation in human
fatty acid amide hydrolase associated with problem drug use. Proc Natl Acad Sci USA 99
(12):8394–8399. doi:10.1073/pnas.082235799 99/12/8394 [pii]
45. Otrubova K, Ezzili C, Boger DL (2011) The discovery and development of inhibitors of fatty
acid amide hydrolase (FAAH). Bioorg Med Chem Lett 21(16):4674–4685. doi:10.1016/j.
bmcl.2011.06.096 S0960-894X(11)00887-0 [pii]
46. Bachovchin DA, Cravatt BF (2012) The pharmacological landscape and therapeutic potential
of serine hydrolases. Nat Rev Drug Discov 11(1):52–68. doi:10.1038/nrd3620 nrd3620 [pii]
Molecular Dynamics Analysis of FAAH Complexed with Anandamide
129