How do benzodiazepines like diazepam exert their anxiolytic effects?

Benzodiazepines, including diazepam, exert their anxiolytic effects primarily by enhancing the activity of gamma-aminobutyric acid (GABA) at GABA-A receptors. GABA is the main inhibitory neurotransmitter in the central nervous system, and when benzodiazepines bind to the benzodiazepine site on the GABA-A receptor, they increase the frequency of chloride channel opening in response to GABA. This results in a greater influx of chloride ions into the neuron, leading to hyperpolarization and a reduced likelihood of neuronal firing. The overall effect is increased inhibition in neural circuits, which is associated with the alleviation of anxiety and the promotion of a calming effect.

Other mechanisms, such as increasing norepinephrine levels or blocking serotonin reuptake, do not contribute to the primary action of benzodiazepines in the same way. Benzodiazepines do not directly alter dopamine receptor activity for their anxiolytic effects, further distinguishing their specific mechanism of action centered around GABA-A receptor modulation.