Benzodiazepines

Abstract

Benzodiazepines are the most widely prescribed central nervous system (CNS) depressants in the United States. They have been in use since the 1960s as anxiolytics, anticonvulsants, and muscle relaxants. The name of the class is derived from the combination of a benzene ring with a seven-membered diazepine ring. Included in the structure is a phenyl ring attached to the 5-position of the diazepine, a requirement for benzodiazepine activity. Benzodiazepines mediate their CNS-depressant activity through the neurotransmitter gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the brain. Benzodiazepines bind to GABAA receptors and potentiate the inhibitory action of GABA. Benzodiazepines have a high therapeutic index and, as a result, rarely cause death by themselves. In addition to the widely prescribed benzodiazepines such as alprazolam, clonazepam, diazepam, and lorazepam, a number of analogs have been developed illicitly, including pyrazolam, flubromazolam, and others. Analysis of benzodiazepines often requires the inclusion of metabolites, depending on the specimen being tested. The chemistry, pharmacology, effects, and analysis of therapeutic and designer benzodiazepines are reviewed.