New endogenous benzodiazepine receptor ligand in human urine: identity with endogenous monoamine oxidase inhibitor?

Normal human urine contains both monoamine oxidase-inhibiting and benzodiazepine receptor-binding material. Each was extracted into ethyl acetate at pH 1 and subjected to high performance liquid chromatography: they ran similarly, showing three major peaks. The correlation coefficient between the pattern of MAO inhibition and inhibition of 3H-flunitrazepam binding to benzodiazepine receptors in the second half of the elution process was 0.78 (p less than 0.001): most UV-absorbing material present was eluted earlier in the run. These results are compatible with, although they do not prove, the hypothesis that the endogenous MAO inhibitor, previously shown to be increased in stress, is also an endogenous inhibitor of 3H-flunitrazepam binding to the benzodiazepine receptor. This material is different from other putative endogenous ligands: it migrates more rapidly than the potent but artefactual beta-carboline-3-carboxylic acid ethyl ester previously isolated from human urine; nor can the effect we have identified derive from harmane, inosine, hypoxanthine or nicotinamide which fail to extract into ethyl acetate at pH 1.