Occurrence of "natural" benzodiazepines

Area of Science:

• Pharmacology
• Biochemistry
• Analytical Chemistry

Background:

• Benzodiazepines (BZD), widely prescribed anxiolytics and hypnotics, are increasingly found in trace amounts in natural sources.
• Evidence suggests BZD may occur naturally in plants, animals, and humans, raising questions about their origin and function.
• The biosynthesis pathway for these naturally occurring BZD remains unknown, with a prevailing hypothesis suggesting a plant origin.

Purpose of the Study:

• To review the evidence for naturally occurring benzodiazepines (BZD) in biological systems.
• To discuss analytical methods used for BZD detection and quantification.
• To explore the potential physiological or biological roles of endogenous BZD.

Main Methods:

• Detection of BZD in various biological matrices using techniques like gas chromatography-mass spectrometry (GC-MS).
• Quantification of BZD using diverse analytical methods, yielding concentration ranges for compounds like diazepam and desmethyldiazepam.
• Investigation of BZD-receptor binding activity in cerebrospinal fluid.

Main Results:

• Trace amounts of various BZD, including diazepam (0.005–1 ng/g) and desmethyldiazepam (0.01–0.5 ng/g), have been identified in plant, animal, and human tissues.
• The physiological significance of these low concentrations is currently speculative.
• High BZD-receptor binding activity was observed in cerebrospinal fluid of patients with advanced hepatic encephalopathy.

Conclusions:

• The presence of BZD in natural sources suggests a potential "endogenous" or "natural" origin.
• Further research is needed to elucidate BZD biosynthesis and definitively establish their sources.
• Solving analytical challenges is crucial for understanding the role of natural BZD in central nervous system regulation.