In 2019, it was the 117th most commonly prescribed medication in the United States, with more than 5 million prescriptions. In 1985 the patent ended, and there are now more than 500 brands available on the market. It is on the World Health Organizations List of Essential Medicines. Medical uses
Diazepam is mainly used to treat anxiety, insomnia, panic attacks and symptoms of acute alcohol withdrawal. It is also used as a premedication for inducing sedation, anxiolysis, or amnesia before certain medical procedures (e.g., endoscopy). In 2020, it was approved for use in the United States as a nasal spray to interrupt seizure activity in people with epilepsy. Diazepam is the most commonly used benzodiazepine for "tapering" benzodiazepine dependence due to the drugs comparatively long half-life, allowing for more efficient dose reduction.
Diazepam also decreases prolactin release in rats. Mechanism of action
Benzodiazepines are positive allosteric modulators of the GABA type A receptors (GABAA). The GABAA receptors are ligand-gated chloride-selective ion channels that are activated by GABA, the major inhibitory neurotransmitter in the brain. Binding of benzodiazepines to this receptor complex promotes the binding of GABA, which in turn increases the total conduction of chloride ions across the neuronal cell membrane. This increased chloride ion influx hyperpolarizes the neurons membrane potential. As a result, the difference between resting potential and threshold potential is increased and firing is less likely. As a result, the arousal of the cortical and limbic systems in the central nervous system is reduced.The GABAA receptor is a heteromer composed of five subunits, the most common ones being two αs, two βs, and one γ (α2β2γ). For each subunit, many subtypes exist (α1–6, β1–3, and γ1–3). GABAA receptors containing the α1 subunit mediate the sedative, the anterograde amnesic, and partly the anticonvulsive effects of diazepam. GABAA receptors containing α2 mediate the anxiolytic actions and to a large degree the myorelaxant effects. GABAA receptors containing α3 and α5 also contribute to benzodiazepines myorelaxant actions, whereas GABAA receptors comprising the α5 subunit were shown to modulate the temporal and spatial memory effects of benzodiazepines. Diazepam is not the only drug to target these GABAA receptors. Drugs such as flumazenil also bind to GABAA to induce their effects.Diazepam appears to act on areas of the limbic system, thalamus, and hypothalamus, inducing anxiolytic effects.