Mechanisms of Action of Benzodiazepines

This chapter discusses the mechanisms of action of benzodiazepines. "Mechanisms" is used in the plural because the actions of a psychotropic agent may be expressed on multiple levels. The greatest progress in revealing the mechanisms of action of benzodiazepines has been at the biochemical level. Biochemical and pharmacological evidence strongly implicates the γ-aminobutyric acid (GABA) synapse as a major site of action of the benzodiazepines. An action on the GABA synapse may account for alterations in the effects of other neurotransmitters, such as norepinephrine, serotonin, and acetylcholine. One of the most ubiquitous neurotransmitters in brain tissue, GABA is known to impinge upon aminergic and cholinergic neurons throughout the CNS. Benzodiazepines may have direct effects on the activity of neurochemicals other than GABA. Two preliminary reports suggest that alterations in GABA sensitivity do not account for all of the pharmacological activity of diazepam. Most drugs that influence the CNS are known to alter the disposition of more than one neurotransmitter, and there is no evidence to suggest that the benzodiazepines act differently.