On the basis of the chemical structures of two previously developed metabolically stable and relatively potent inhibitors of anandamide uptake, OMDM-1,2, two series of potential covalent inhibitors of anandamide cellular reuptake, which might be used for the molecular characterization of the protein(s) involved in the membrane transport of endocannabinoids, have been designed and synthesized. Most of the compounds inhibited uptake to a varied extent and in a generally enantio-sensitive manner when co-incubated with [(14)C]anandamide, but only three of them, the photoactivatable 1a (OMDM-37), 1b (OMDM-39), and 8(Lo395), also produced a significant inhibition of uptake following the preincubation only of the cells, and this effect was significantly enhanced following UV exposure only in the case of 8. None of the new compounds inhibited [(14)C]anandamide hydrolysis with IC(50) < 50 microM, except for 1b.