Mechanism of action<unk>  enhances the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system to give its anticonvulsant, skeletal muscle relaxant, and anxiolytic effects. It acts by binding to the benzodiazepine site of the GABA receptors, which enhances the electric effect of GABA binding on neurons, resulting in an increased influx of chloride ions into the neurons. This further results in an inhibition of synaptic transmission across the central nervous system. Benzodiazepines do not have any effect on the levels of GABA in the brain.<unk>  has no effect on GABA levels and has no effect on gamma-aminobutyric acid transaminase.<unk>  does, however, affect glutamate decarboxylase activity. It differs from other anticonvulsant drugs it was compared to in a study.<unk> 's primary mechanism of action is the modulation of GABA function in the brain, by the benzodiazepine receptor, located on GABAA receptors, which, in turn, leads to enhanced GABAergic inhibition of neuronal firing. Benzodiazepines do not replace GABA, but instead enhance the effect of GABA at the GABAA receptor by increasing the opening frequency of chloride ion channels, which leads to an increase in GABA's inhibitory effects and resultant central nervous system depression. In addition,<unk>  decreases the utilization of 5-HT (serotonin) by neurons and has been shown to bind tightly to central-type benzodiazepine receptors. Because<unk>  is effective in low milligram doses (0.5 mg<unk>  = 10 mg diazepam), it is said to be among the class of "highly potent" benzodiazepines. The anticonvulsant properties of benzodiazepines are due to the enhancement of synaptic GABA responses, and the inhibition of sustained, high-frequency repetitive firing. Benzodiazepines, including<unk> , bind to mouse glial cell membranes with high affinity.<unk>  decreases release of acetylcholine in the feline brain and decreases prolactin release in rats. Benzodiazepines inhibit cold-induced thyroid-stimulating hormone (also known as TSH or thyrotropin) release. Benzodiazepines act via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit depolarization-sensitive calcium uptake in experimentation on rat brain cell components. This has been conjectured as a mechanism for high-dose effects on seizures in the study.<unk>  is a 2'-chlorinated derivative of nitrazepam, which increases its potency due to electron-attracting effect of the halogen in the ortho-position. Pharmacokinetics<unk>  is lipid-soluble, rapidly crosses the blood–brain barrier, and penetrates the placenta. It is extensively metabolised into pharmacologically inactive metabolites, with only 2% of the unchanged drug excreted in the urine.<unk>  is metabolized extensively via nitroreduction by cytochrome P450 enzymes, including CYP3A4. Erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, cimetidine, and grapefruit juice are inhibitors of CYP3A4 and can affect the metabolism of benzodiazepines. It has an elimination half-life of 19–60 hours. Peak blood concentrations of 6.5–13.5 ng/mL were usually reached within 1–2 hours following a single 2 mg oral dose of micronized<unk>  in healthy adults. In some individuals, however, peak blood concentrations were reached at 4–8 hours.<unk>  passes rapidly into the central nervous system, with levels in the brain corresponding with levels of unbound<unk>  in the blood serum.<unk>  plasma levels are very unreliable amongst patients. Plasma levels of<unk>  can vary as much as tenfold between different patients.<unk>  has plasma protein binding of 85%.<unk>  passes through the blood–brain barrier easily, with blood and brain levels corresponding equally with each other. The metabolites of<unk>  include 7-aminoclonazepam, 7-acetaminoclonazepam and 3-hydroxy<unk> . These metabolites are excreted by the kidney. It is effective for 6–8 hours in children, and 6–12 in adults.
Clonazepam
Diclazepam
Halazepam
Clotiazepam
Phenazepam
Oxazepam
Medazepam
Gidazepam