New developments on the search for the endogenous ligand(s) of central benzodiazepine receptors.

This review describes three new research developments that have occurred since 1983, in relation to the possible identification of endogenous ligand(s) for the benzodiazepine central receptor (BZD-R). The polypeptides diazepam binding inhibitor (DBI) and the ODN of Guidotti and Costa, as well as the endozepines of Shoyab and Todaro are considered in their affinities and pharmacological actions. The work of the De Blas group on the presence of benzodiazepines in brain, confirmed by us and other groups, is commented and the discovery, in our own laboratory, of n-butyl-?-carboline-3-carboxylate as a possible putative ligand, having high affinity for the BZD-R and showing proconvulsant and "anxiogenic" properties, is described. In the concluding remarks, the possibility that two or more endogenous ligands with opposing activity could regulate the BZD-GABA receptor complex is postulated.