The Fatty Acid Amide Hydrolase Inhibitor URB597 (Cyclohexylcarbamic Acid 3′-Carbamoylbiphenyl-3-yl Ester) Reduces Neuropathic Pain after Oral Administration in Mice

@article{Russo2007TheFA,
  title={The Fatty Acid Amide Hydrolase Inhibitor URB597 (Cyclohexylcarbamic Acid 3′-Carbamoylbiphenyl-3-yl Ester) Reduces Neuropathic Pain after Oral Administration in Mice},
  author={Roberto Russo and Jesse Loverme and G. La Rana and Timothy R Compton and Jeff A. Parrott and Andrea Duranti and Andrea Tontini and Marco Mor and Giorgio Tarzia and Antonio Calignano and Daniele Piomelli},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2007},
  volume={322},
  pages={236 - 242}
}
Fatty acid amide hydrolase (FAAH) is an intracellular serine hydrolase that catalyzes the cleavage of bioactive fatty acid ethanolamides, such as the endogenous cannabinoid agonist anandamide. Genetic deletion of the faah gene in mice elevates brain anandamide levels and amplifies the antinociceptive effects of this compound. Likewise, pharmacological blockade of FAAH activity reduces nocifensive behavior in animal models of acute and inflammatory pain. In the present study, we investigated the… 

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References

SHOWING 1-10 OF 42 REFERENCES

Characterization of the Fatty Acid Amide Hydrolase Inhibitor Cyclohexyl Carbamic Acid 3′-Carbamoyl-biphenyl-3-yl Ester (URB597): Effects on Anandamide and Oleoylethanolamide Deactivation

The results suggest that an enzyme distinct from FAAH catalyzes OEA hydrolysis in the duodenum, where this lipid substance acts as a local satiety factor.

Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain

Spinal administration of URB597 attenuated evoked responses of spinal neurons and elevated levels of endocannabinoids in sham-operated and SNL rats suggest that peripheral FAAH activity may be altered or that alternative pathways of metabolism have greater importance in SNL Rats.

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.

Fatty acid amide hydrolase (FAAH) is a promising target for modulating endocannabinoid and fatty acid ethanolamide signaling, which may have important therapeutic potential. We recently described a

Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models

It is suggested that the FAAH inhibitor URB597 produces cannabinoid CB1 and CB2 receptor‐mediated analgesia in inflammatory pain states, without causing the undesirable side effects associated with cannabinoid receptor activation.

Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597).

KDS-4103 acts by enhancing the tonic actions of anandamide on a subset of CB(1) receptors, which may normally be engaged in controlling emotions and pain, to offer a novel approach with a favorable therapeutic window for the treatment of anxiety, depression and pain.

Molecular Characterization of a Phospholipase D Generating Anandamide and Its Congeners*

It is confirmed that a specific phospholipase D is responsible for the generation of N-acylethanolamines including anandamide, strongly suggesting the physiological importance of lipid molecules of this class.

Rapid Broad-Spectrum Analgesia through Activation of Peroxisome Proliferator-Activated Receptor-α

It is reported that agonists of the nuclear receptor PPAR-α (peroxisome proliferator-activated receptor-α) suppress pain behaviors induced in mice by chemical tissue injury, nerve damage, or inflammation and may represent a novel class of analgesics.