Numerous analogs of arachidonoyl ethanolamide (AEA, anandamide)1 potentiate its biological activity. This potentiation is ascribed either to inhibition of AEA reuptake into neurons, or inhibition of fatty acid amide hydrolase (FAAH) within the neurons.2 One of the more potent and selective reuptake inhibitors is UCM707, a 3-furyl arachidonoyl analog. UCM707 has an IC50 of 0.8 µM for the inhibition of tritiated AEA uptake into human U937 cells but has low affinity for FAAH, exhibiting an IC50 value of 30 µM.3 UCM707 also potentiates the biological effects of AEA when co-administered in rats.4
1
Devane, W.A., Hanus, L., Breuer, A., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science2581946-1949(1992).
2
Deutsch, D.G., Glaser, S.T., Howell, J.M., et al. The cellular uptake of anandamide is coupled to its breakdown by fatty-acid amide hydrolase. J Biol Chem276(10)6967-6973(2001).
3
López-Rodriguez, M.L., Viso, A., Ortega-Gutiérrez, S., et al. Design, synthesis, and biological evaluation of new endocannabinoid transporter inhibitors. Eur J Med Chem38403-412(2003).
4
de Lago, E., Fernandez-Ruiz, J., Ortega-Gutiérrez, S., et al. UCM707, a potent and selective inhibitor of endocannabinoid uptake, potentiates hypokinetic and antinociceptive effects of anandamide. Eur J Pharmacol44999-103(2002 Jun 20).
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Devane, W.A., Hanus, L., Breuer, A., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science2581946-1949(1992).
Deutsch, D.G., Glaser, S.T., Howell, J.M., et al. The cellular uptake of anandamide is coupled to its breakdown by fatty-acid amide hydrolase. J Biol Chem276(10)6967-6973(2001).
López-Rodriguez, M.L., Viso, A., Ortega-Gutiérrez, S., et al. Design, synthesis, and biological evaluation of new endocannabinoid transporter inhibitors. Eur J Med Chem38403-412(2003).
de Lago, E., Fernandez-Ruiz, J., Ortega-Gutiérrez, S., et al. UCM707, a potent and selective inhibitor of endocannabinoid uptake, potentiates hypokinetic and antinociceptive effects of anandamide. Eur J Pharmacol44999-103(2002 Jun 20).