Naturally occurring benzodiazepines: current status of research and clinical implications

Naturally occurring benzodiazepines (BZDs) were first detected in mammalian tissues in 1986. They comprise a variety of 1,LF-benzodiazepines correspon ding to drugs commercially available for the treatment of anxiety disorders , sleep disturbances and epileptic seizures. Several biosynthetic pathways leading to the formation of BZDs are currently being discussed and have led to the proposition of possible precursor molecules. For years, the identification of naturally occurring BZDs in mammalian orga nisms was mostly confined to post mortem CNS material for sensitivity reaso ns. While radioimmunoassay and radioreceptorassay techniques have been tent atively applied to quantitations of genuine BZDs from human milk and cerebr ospinal fluid, accurate measurements in peripheral blood have only recently become accessible, e.g., by gas chromatography/selected ion monitoring-mas s spectrometry (GC/SIM-MS). This review summarizes existing evidence of ben zodiazepines' occurrence in nature and discusses implications for neuropsyc hiatric disorders.