β-Carboline-3-carboxylic acid ethyl ester antagonizes diazepam activity

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Abstract
Analogous to the progression of events in the opiate receptor-enkephalin area, the 1st reports that benzodiazepines have selective and specific high-affinity binding sites in brain have stimulated a search for the endogenous ligand or substance that might normally act at these sites. Braestrup and co-workers have extracted from human urine a .gamma.-fraction which they have recently identified as .beta.-carboline-3-carboxylic acid ethyl ester (.beta.CEE). This substance is reported to be extremely potent in displacing 3H-diazepam from brain binding sites and it is proposed that a .beta.-carboline-3-carboxylic acid derivative might, in part, be the endogenous ligand for the brain benzodiazepine receptor. Several synthetically derived .beta.-carboline-3-carboxylic acid analogs were studied. Data obtained from testing only the .beta.CEE described by Braestrup are presented. In addition to confirming these workers'' observation that this compound is a potent displacer of 3H-diazepam from brain tissue, these pharmacological data indicate that .beta.CEE has activity that is opposite to, rather than similar to, that of diazepam.
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