Benzodiazepine receptors endogenous ligands

Basile AS, Gammal SH, Jones EA, Skolnick P GABA-A receptor complex in an experimental model of hepatic encephalopathy Evidence for elevated levels of an endogenous benzodiazepine receptor complex ligand. J Neurochem 1989 53 1057-1063. 

Another possibility that may account for an increase or decrease in the anxiety state relates to the presence of endogenous ligands that act on the benzodiazepine receptors. These ligands have been called endozepines and although a number of compounds have been isolated from mammalian brain it is uncertain whether the endogenous concentration is sufficiently high for them to modulate GABA-A receptor or benzodiazepine receptor function. 

THE QUEST FOR THE ENDOGENOUS BENZODIAZEPINE RECEPTOR LIGAND ( ENDOZEPINES )... 

Table 19.4 Putative endogenous ligands for the benzodiazepine binding domain on the GABAa receptor...

Although, by analogy with the opioids, one would expect there to be an endogenous ligand for the widely distributed benzodiazepine receptor, its existence remains uncertain and we must be alert to the possibility that any such ligand(s) could have either agonist or inverse agonist activity. 

The undisputed efficacy of benzodiazepines in relief of anxiety led to the question of whether this disorder could arise from abnormal concentrations in the brain of an endogenous ligand or a malfunction of the benzodiazepine/GABA receptor system. An important study, aimed at distinguishing between these possibilities, has been carried out in humans (Nutt et al. 1990) and was based on the premise that anxiety could be caused by either ... 

Inadequate activity of an endogenous ligand which is a benzodiazepine receptor agonist and suppresses anxiety. In this case, the administration of the antagonist, fiumazenil, should induce anxiety in normal subjects and exacerbate anxiety in anxious patients. 

De Robertis, E, Pena, C, Paladini, AC and Medina, JH (1988) New developments on the search for endogenous ligand(s) of central benzodiazepine receptors. Neurochem. Int. 13 1-11. 

Substances with a neuromodulatory effect on brain neurotransmitters by direct actions of specific receptors that modify the actions of the transmitters listed include prostaglandins, adenosine, enkephalins, substance P, cholecystokinin, endorphins, endogenous benzodiazepine receptor ligands, and possibly histamine. CNS, central nervous system. NMDA, N-methyl-D-aspartate. Strych, strychnine. 

Cinone, N., Holtje, H.-D., Carotti, A. Development of a Unique 3D Interaction Model of Endogenous and Synthetic Peripheral Benzodiazepine Receptor Ligands. /. Comput.-Aided Mol. Des. 2000, 14, 753-768. 

Table 9.2. Putative endogenous ligands for the benzodiazepine receptor in the mammalian brain...

Guidotti and Ferrero95 isolated from human and rat brain extracts neuroactive peptides that interact with the receptors at which benzodiazepines (e.g. Valium and Librium) induce biological effects. The DBI peptide 48 ( anxiety peptide ), an endogenous ligand of the benzodiazepine receptor, causes anxiety, in contrast to the benzodiazepines. 

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