A potent FAAH inhibitor
URB937 is a potent fatty acid amide hydrolase (FAAH) inhibitor (IC50 = 26.8 nM, in vitro) that does not penetrate the blood-brain barrier, thus preventing arachidonoyl ethanolamide deactivation only in peripheral tissues.[1]? Its ED50 value for FAAH inhibition in brain is 200-fold higher than the ED50 value for FAAH inhibition in liver when administered systemically in mice (40 mg/kg versus 0.2 mg/kg, respectively). Subcutaneous administration of URB937 reduces acetic acid-induced writhing in mice with an ED50 value of 0.1 mg/kg. A single 1 mg/kg injection of URB937 sufficiently attenuates behavioral responses elicited in mouse models of neuropathic and inflammatory pain. As a peripherally-specific FAAH inhibitor, URB937 may offer an alternative approach to pain therapy devoid of unwanted central effects.
参考文献:
[1]. Clapper, J.R., Moreno-Sanz, G., Russo, R., et al. Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism Nat. Neurosci. 13(10), 1265-1270 (2010).
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