Naturally occurring benzodiazepines and benzodiazepine-like molecules in brain

Great progress has been made in the last five years in demonstrating the presence of benzodiazepines (BZDs) in mammalian tissues, in beginning studies on the origin of these natural compounds and in elucidating their possible biological roles. Many unanswered questions remain regarding the sources and the biosynthetic pathways responsible for the presence of BZDs in brain and their different physiological and/or biochemical actions. This essay will focus on recent findings supporting that: (1) BZDs are of natural origin; (2) mammalian brain contains BZDs in concentrations ranging between 5.10(-10) to 10(-8) M; (3) BZDs and BZD-like molecules are unevenly distributed in brain; the highest concentration is found in limbic structures (4) dietary source of BZDs might be a plausible explanation for their occurrence in animal tissues, including man; (5) the formation of BZDs-like molecules in brain is a possibility, experimentally supported; (6) BZDs like molecules including diazepam and N desmethyldiazepam are elevated in hepatic encephalopathy; (7) natural BZDs in the brain are involved in the modulation of memory processes. Future studies using the full range of biochemical, physiological, behavioral and molecular biological techniques available to the neuroscientist will hopefully continue to yield new and exciting information concerning the biological roles that BZDs might play in the normal and pathological functioning of the brain.