Searching for endogenous ligand(s) of central benzodiazepine receptors.

The discovery, in 1977, of the specific binding sites for benzodiazepines in the brain of mammals, notably in man, lends support to the possible existence of endogenous compounds acting as natural ligands of these sites. At present, more than a dozen of molecules with the capacity to displace bound [(3)H]benzodiazepines from their specific sites have been extracted from the brain of several species (rat, pig, bovine), the cerebrospinal fluid and urine of man. These molecules are proteins, peptides, purines, ?-carbolines and exhibit (some) pharmacological properties similar or opposite to those of benzodiazepines. The most recent data concerning benzodiazepine receptors suggest that the endogenous ligand would be, if it exists, a benzodiazepine-like compound (agonist) with an indolic structure.