From the Guidelines
Benzodiazepines primarily work by enhancing the effect of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, by activating γ-aminobutyric acid A (GABA) neuronal receptors, as stated in the most recent guidelines 1.
Mechanism of Action
The primary mechanism of action of benzodiazepines involves binding to a specific site on the GABA-A receptor complex, which increases the frequency of chloride ion channel opening, leading to hyperpolarization of the neuronal membrane, making neurons less excitable and thus producing anxiolytic, sedative, muscle relaxant, and anticonvulsant effects 1.
Key Points
- Benzodiazepines have anxiolytic, amnestic, sedating, hypnotic, and anticonvulsant effects, but no analgesic activity 1.
- The potency and duration of action differ among benzodiazepines due to variations in their pharmacokinetic properties, particularly their lipid solubility and presence of active metabolites 1.
- Benzodiazepines can cause physical dependence with prolonged use, typically after 2-4 weeks of regular administration, and should generally be prescribed for short-term use when possible to minimize risks of tolerance and withdrawal 1.
Clinical Considerations
- Benzodiazepine overdose causes CNS depression through agonist effects at the GABA-A receptor with resultant respiratory compromise through loss of protective airway reflexes 1.
- Flumazenil, a competitive antagonist at the benzodiazepine binding site on the GABA-A receptor, reverses CNS and respiratory depression, potentially preventing the need for intubation and mechanical ventilation, but may precipitate refractory benzodiazepine withdrawal and seizures in patients with benzodiazepine tolerance 1.
From the FDA Drug Label
CLINICAL PHARMACOLOGY Pharmacodynamics CNS agents of the 1,4 benzodiazepine class presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system. The primary mechanism of action of benzodiazepine is binding to stereo specific receptors at several sites within the central nervous system.
- The exact mechanism of action is unknown. 2
From the Research
Mechanism of Action of Benzodiazepine
The primary mechanism of action of benzodiazepine involves the modulation of the GABA (gamma-aminobutyric acid) receptor, which is an inhibitory neurotransmitter in the central nervous system. Key aspects of this mechanism include:
- Allosteric modulation of the GABAA receptor to enhance the activity of GABA, resulting in a slowing of neurotransmission and sedative and anxiolytic effects 3
- Increasing the affinity of the GABA receptor for its ligand, thereby augmenting the inhibitory effect of a given concentration of GABA 4
- Facilitating neurotransmission in GABAergic synapses, probably by increasing the affinity of the GABA receptor to GABA 5
- Influence on the turnover rate of GABA in rat brain nuclei, with benzodiazepines such as diazepam acting as GABA-mimetic drugs 6
GABAA Receptor Subunit-Specific Effects
Recent studies have shown that not all GABAA receptors function in the same manner, with those containing α1 subunits associated with sleep regulation and those containing α2 and/or α3 subunits associated with anxiety phenomena 7. The selectivity profile of anxiolytic drugs, such as chlornordiazepam, the main active metabolite of mexazolam, can have a significant clinical impact, with evidence suggesting that mexazolam has a "pharmacodynamic fingerprint" that correlates better with an anxiolytic profile and fewer sedative effects compared to other anxiolytic benzodiazepines 7.