López-Rodríguez María L, Viso Alma, Ortega-Gutiérrez Silvia, Fowler Christopher J, Tiger Gunnar, de Lago Eva, Fernández-Ruiz Javier, Ramos José A
Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense, E-28040 Madrid, Spain.
J Med Chem. 2003 Apr 10;46(8):1512-22. doi: 10.1021/jm0210818.
A new series of arachidonic acid derivatives were synthesized and evaluated as inhibitors of the endocannabinoid uptake. Most of them are able to inhibit anandamide uptake with IC(50) values in the low micromolar range (IC(50) = 0.8-24 microM). In general, the compounds had only weak effects upon CB(1), CB(2), and VR(1) receptors (K(i) > 1000-10000 nM). In addition, there was no obvious relationship between the abilities of the compounds to affect anandamide uptake and to inhibit anandamide metabolism by fatty acid amidohydrolase (FAAH; IC(50) = 30-113 microM). This indicates that the compounds do not exert their effects secondarily to FAAH inhibition. It is hoped that these compounds, particularly the most potent in this series (compound 5, UCM707, with IC(50) values for anandamide uptake and FAAH of 0.8 and 30 microM, respectively), will provide useful tools for the elucidation of the role of the anandamide transporter system in vivo.
合成了一系列新的花生四烯酸衍生物，并对其作为内源性大麻素摄取抑制剂进行了评估。它们中的大多数能够抑制花生四烯乙醇胺摄取，IC(50)值处于低微摩尔范围（IC(50)=0.8 - 24 microM）。一般来说，这些化合物对CB(1)、CB(2)和VR(1)受体只有微弱作用（K(i)>1000 - 10000 nM）。此外，化合物影响花生四烯乙醇胺摄取的能力与抑制脂肪酸酰胺水解酶（FAAH；IC(50)=30 - 113 microM）催化花生四烯乙醇胺代谢的能力之间没有明显关系。这表明这些化合物并非通过抑制FAAH而间接发挥作用。希望这些化合物，特别是该系列中最有效的化合物（化合物5，UCM707，花生四烯乙醇胺摄取和FAAH的IC(50)值分别为0.8和30 microM），将为阐明花生四烯乙醇胺转运体系统在体内的作用提供有用工具。
