Benzodiazepine Receptors

It appeared recently that the important group of psychoactive drugs, the benzodiazepines, binds with high affinity to a single class of saturable sites on brain membranes of all higher vertebrates including man. There was a good correlation between the pharmacological effects of different benzodiazepines and their affinity for 3H-diazepam and 3H-flunitrazepam binding sites, indicating that the binding site is the physiological relevant receptor upon which benzodiazepines act. The most active benzodiazepines, like lorazepam and triazolam, act in concentrations of about 1 nmol/l. The highest concentration of benzodiazepine receptors in human brain was found in cerebral cortical regions, intermediate levels were found in midbrain and some limbic structures, while white matter areas exhibit low levels. This indicates that benzodiazepines act preferentially in cortical areas. The presence of benzodiazepine receptors suggests that there may an endogenous ligand for these receptors. Hypoxanthine, inosine and nicotinamide have been isolated from brain tissue and proposed as endogenous ligands. These three compounds are very weak on benzodiazepine receptors. The most promising compound has been isolated from human urine and brain and is a lipophilic, small-molecular weight aromatic compound, which exhibits very high affinity (Ki congruent to 0.003 mumol/l) for benzodiazepine receptors.