Endocannabinoids transporter

Alexander JP, Cravatt BF (2006) The putative endocannabinoid transport blocker LY2183240 is a potent inhibitor of FAAH and several other brain serine hydrolases. J Am Chem Soc 128(30) 9699-9704... 

Chesterfield AK, Moore SA, Schober DA, et al (2005) Pharmacological characterization of the endocannabinoid transporter using a novel high affinity hgand. XV Conference of the International Cannabinoid Research Society, Clearwater Beach, 24-27 June 2005. International Cannabinoid Research Society, Burlington, p 9... 

Hajos N, Kathuria S, Dinh T, Piomelh D, Freund TF (2004) Endocannabinoid transport tightly controls 2-arachidonoyl glycerol actions in the hippocampus effects of low temperature and the transport inhibitor AM404. Eur J Neurosci 19 2991-2996... 

Lopez-RodriguezML, Viso A, Ortega-Gutierrez S, Lastres-Becker I, Gonzalez S, Fernandez-Ruiz JJ, Ramos, JA (2001) Design, synthesis and biological evaluation of novel arachidonic acid derivatives as highly potent and selective endocannabinoid transporter inhibitors. J Med Chem 44 4505-4508... 

Despite the fact that the endocannabinoid transporter has not yet been isolated or cloned, a situation that has led to some controversy about its existence (Glaser et al. 2003), there are several anandamide analogs that behave in vitro as endocannabinoid transport inhibitors (Giuffrida et al. 2001) and that, in vivo, produce significant effects on motor function (for review see Ferndndez-Ruiz et al. 2002). 

The antinociceptive activity of the endocannabinoid transporter and, particularly, FAAH inhibitors has been mentioned earlier. This effect, however, has been mostly studied using the hot plate paradigm of acute pain, which is not very relevant to the most frequent types of chronic, inflammatory,... 

A variety of synthetic compounds have been tested for their ability to interfere with endocannabinoid transport. Among them, the first reported anandamide transporter inhibitor, A-(4-hydroxyphenyl)arachidonoyl amide (AM404, Figure 7) (Beltramo et aL, 1997), stands out for its relatively high potency and its ability to block endocannabinoid transport both in vitro and in vivo, AM404... 

Sanson B, Wang T, Sun J, et al. Crystallographic study of FABP5 as an intracellular endocannabinoid transporter. Acta Crystallogr D Biol Crystallogr. 2014 70(Pt 2) 290-298. 

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