Although βCCE and other β-carbolines are not endogenous BZR
ligands (vide supra) and are not currently approved for clinical use, they are used to characterize different
GABAA/BZR subtypes (based on a and g subunit composition) and function (e.g., the partial agonist abecarnil)
toward the discovery of anxioselective drugs. In this regard, the β-carboline ring system is planar in comparison
to the boat conformation of the 1,4-benzodiazepines; thus, β-carbolines
have been useful to extend structure–activity relationship information for the agonist, antagonist, and inverse
agonist pharmacophores of the various GABAA/BZR subtypes.
Several β-carbolines have approximately 10-fold higher affinity for the BZR when compared to diazepam. The ethyl
ester of β-carboline-3-carboxylic acid (βCCE), identified in human urine extracts as an artifact of the extraction
procedure, has very high affinity for the BZR.
