Cell lines

Rat brain cortical neurons

Preparation method

The solubility of this compound in DMSO is >16.9 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

10 nM

Applications

URB597 selectively inhibited the breakdown of [3H]anandamide without reducing its carrier-mediated uptake, which caused non-metabolized [3H]anandamide to accumulate in, and finally exit from the cortical neurons. The accumulated [3H]anandamide was released from the neurons back into the media via passive diffusion rather than reverse transport.

Animal models

Rats

Dosage form

0.3 mg/kg; i.p.

Applications

In rats, URB597 rapidly inhibited FAAH (< 15 mins) and its inhibitory effect could last for over 12 hrs. Meanwhile, the contents of anandamide and other fatty-acid ethanolamides were significantly elevated in brain. In addition, URB597 markedly enhanced the hypothermic response caused by a sub-threshold dose of anandamide (5 mg/kg; i.p.). However, when injected alone, URB597 showed no effect on body temperature.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

URB597, also known as KDS-4103, is a potent and selective inhibitor of fatty-acid amide hydrolase (FAAH), an enzyme catalyzing the intracellular hydrolysis of the endocannabinoid anandamide, with values of 50% inhibition concentration IC₅₀of 5 nM and 3 nM in rat brain membranes and human liver microsomes respectively. Study results have shown that, through intraperitoneal (i.p.) administration, URB597 potently inhibits FAAH in rat brain with a median inhibitory dose ID₅₀of 0.15 mh/kg. However, URB597 fails to show significant inhibition against a few other cannabinoid-related targets (such as cannabinoid receptors and anandamide transport) as well as a broad range of receptors, ion channels, transporters and enymes.

Reference

[1].Daniele Piomelli, Giorgio Tarzia, Andrea Duranti, Andrea Tontini, Marco Mor, Timothy R. Compton, Oliver Dasse, Edward P. Monaghan, Jeff A. Parrot and David Putman. Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS Drug Review 2006; 12(1): 21-38