Description

Diazepam is a long-acting benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnestic properties.

The exact sites and mode of action of the benzodiazepines have not been fully elucidated, but the effects of the drugs appear to be mediated through the inhibitory neurotransmitter γ-aminobutyric acid (GABA). The drugs appear to act at the limbic, thalamic, and hypothalamic levels of the CNS, producing anxiolytic, sedative, hypnotic, skeletal muscle relaxant, and anticonvulsant effects. Benzodiazepines are capable of producing all levels of CNS depression—from mild sedation to hypnosis to coma. Specific binding sites with high affinity for benzodiazepines have been detected in the CNS, and the affinity of these sites for the drugs is enhanced by both GABA and chloride. The sites and actions of benzodiazepines within the CNS appear to involve a macromolecular (oligomer or possibly a tetramer) complex (GABAA-receptor-chloride ionophore complex) that includes GABAA receptors (GABA recognition sites), high-affinity benzodiazepine receptors, and chloride channels, although precise relationships between the sites of action of benzodiazepines and GABA-regulated (-gated) chloride channels remain to be more fully elucidated. Allosteric interactions of central benzodiazepine receptors with GABAA receptors and subsequent opening of chloride channels appear to be involved in eliciting the CNS effects of the drugs; the benzodiazpine receptors act as modulatory sites on the complex. Anxiolytic and possibly paradoxical CNS stimulatory effects of benzodiazepines are postulated to result from release of previously suppressed responses (disinhibition). After usual doses of benzodiazepines for several days, the drugs cause a moderate decrease in rapid eye movement (REM) sleep. REM rebound does not occur when the drugs are withdrawn. Stage 3 and 4 sleep are markedly reduced by usual doses of the drugs; the clinical importance of these sleep stage alterations has not been established. Benzodiazepines appear to produce skeletal muscle relaxation predominantly by inhibiting spinal polysynaptic afferent pathways, but the drugs may also inhibit monosynaptic afferent pathways. The drugs may inhibit monosynaptic and polysynaptic reflexes by acting as inhibitory neuronal transmitters or by blocking excitatory synaptic transmission. The drugs may also directly depress motor nerve and muscle function.