PMID- 26310614
OWN - NLM
STAT- MEDLINE
DCOM- 20160915
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 5
DP  - 2015 Aug 27
TI  - Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor 
      F96 through PPAR-alpha.
PG  - 13565
LID - 10.1038/srep13565 [doi]
LID - 13565
AB  - Pharmacological blockade of N-acylethanolamine acid amidase (NAAA) activity is an 
      available approach for inflammation and pain control through restoring the 
      ability of endogenous PEA. But the recently reported NAAA inhibitors suffer from 
      the chemical and biological unstable properties, which restrict functions of NAAA 
      inhibition in vivo. It is still unrevealed whether systematic inhibition of NAAA 
      could modulate PEA-mediated pain signalings. Here we reported an oxazolidinone 
      imide compound 3-(6-phenylhexanoyl) oxazolidin-2-one (F96), which potently and 
      selectively inhibited NAAA activity (IC50 = 270 nM). Intraperitoneal (i.p.) 
      injection of F96 (3-30 mg/kg) dose-dependently reduced ear edema and restored PEA 
      levels of ear tissues in 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced ear 
      edema models. Furthermore, F96 inhibited acetic acid-induced writhing and 
      increased spared nerve injury induced tactile allodynia thresholds in a 
      dose-dependent manner. Pharmacological effects of F96 (10 mg/kg, i.p.) on various 
      animal models were abolished in PPAR-alpha(-/-) mice, and were prevented by PPAR-alpha 
      antagonist MK886 but not by canabinoid receptor type 1 (CB1) antagonist 
      Rimonabant nor canabinoid receptor type 2 (CB2) antagonist SR144528. Zebrafish 
      embryos experiments showed better security and lower toxicity for F96 than 
      ibuprofen. These results revealed that F96 might be useful in treating 
      inflammatory and neuropathic pain by NAAA inhibition depending on PPAR-alpha 
      receptors.
FAU - Yang, Longhe
AU  - Yang L
AD  - Medical College, Xiamen University, Xiamen, Fujian 361005, P. R. China.
AD  - Engineering Research Center of Marine Biological Resource Comprehensive 
      Utilization, Third Institute of Oceanography , State Oceanic Administration, 
      Xiamen, Fujian 361005, P. R. China.
FAU - Li, Long
AU  - Li L
AD  - Medical College, Xiamen University, Xiamen, Fujian 361005, P. R. China.
AD  - Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian 
      Province, College of Chemistry and Chemical Engineering, Xiamen University, 
      Xiamen, Fujian 361005, P. R. China.
FAU - Chen, Ling
AU  - Chen L
AD  - Medical College, Xiamen University, Xiamen, Fujian 361005, P. R. China.
FAU - Li, Yanting
AU  - Li Y
AD  - Medical College, Xiamen University, Xiamen, Fujian 361005, P. R. China.
FAU - Chen, Huixia
AU  - Chen H
AD  - Medical College, Xiamen University, Xiamen, Fujian 361005, P. R. China.
FAU - Li, Yuhang
AU  - Li Y
AD  - Medical College, Xiamen University, Xiamen, Fujian 361005, P. R. China.
FAU - Ji, Guangnian
AU  - Ji G
AD  - Medical College, Xiamen University, Xiamen, Fujian 361005, P. R. China.
FAU - Lin, Donghai
AU  - Lin D
AD  - Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian 
      Province, College of Chemistry and Chemical Engineering, Xiamen University, 
      Xiamen, Fujian 361005, P. R. China.
FAU - Liu, Zuguo
AU  - Liu Z
AD  - Medical College, Xiamen University, Xiamen, Fujian 361005, P. R. China.
FAU - Qiu, Yan
AU  - Qiu Y
AD  - Medical College, Xiamen University, Xiamen, Fujian 361005, P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150827
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (3-(6-phenylhexanoyl)oxazolidin-2-one)
RN  - 0 (Analgesics)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ethanolamines)
RN  - 0 (Fatty Acids)
RN  - 0 (N-acylethanolamines)
RN  - 0 (Oxazolidinones)
RN  - 0 (PPAR alpha)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.4 (amidase)
RN  - Q40Q9N063P (Acetic Acid)
SB  - IM
MH  - Acetic Acid
MH  - Amidohydrolases/*antagonists & inhibitors/metabolism
MH  - Analgesics/chemistry/*pharmacology/therapeutic use
MH  - Animals
MH  - Disease Models, Animal
MH  - Ear/pathology
MH  - Edema/complications/drug therapy
MH  - Enzyme Inhibitors/chemistry/*pharmacology
MH  - Ethanolamines/*metabolism
MH  - Fatty Acids/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuralgia/drug therapy/etiology
MH  - Oxazolidinones/chemistry/*pharmacology/therapeutic use
MH  - PPAR alpha/*metabolism
MH  - RAW 264.7 Cells
MH  - Sciatic Nerve/injuries/pathology
MH  - Zebrafish
PMC - PMC4550851
EDAT- 2015/08/28 06:00
MHDA- 2016/09/16 06:00
PMCR- 2015/08/27
CRDT- 2015/08/28 06:00
PHST- 2015/03/18 00:00 [received]
PHST- 2015/07/30 00:00 [accepted]
PHST- 2015/08/28 06:00 [entrez]
PHST- 2015/08/28 06:00 [pubmed]
PHST- 2016/09/16 06:00 [medline]
PHST- 2015/08/27 00:00 [pmc-release]
AID - srep13565 [pii]
AID - 10.1038/srep13565 [doi]
PST - epublish
SO  - Sci Rep. 2015 Aug 27;5:13565. doi: 10.1038/srep13565.