Binding at the α1β3γ2 GABAA receptor.<unk>  with red space-filling carbon atoms. γ2 receptor subunit in mint green. The α1' subunit is hidden.<unk>  is a positive allosteric modulator of the gamma-aminobutyric acid (GABA) type A receptor. When it binds to the receptor, effects of GABA are enhanced leading to inhibition of neurons in the brain. This results in effects including reduced anxiety, muscle relaxant, antidepressant and anticonvulsant activity. The activity of<unk>  in the central nervous system is dose dependent. Mechanism of action<unk>  is classed as a high-potency triazolobenzodiazepine: a benzodiazepine with a triazole ring attached to its structure. As a benzodiazepine,<unk>  produces a variety of therapeutic and adverse effects by binding to the GABAA benzodiazepine receptor site and modulating its function; GABA receptors are the most prolific inhibitory receptor within the brain. The GABA chemical and receptor system mediates inhibitory or calming effects of<unk>  on the nervous system. Binding of<unk>  to the GABAA receptor, a chloride ion channel, enhances the effects of GABA, a neurotransmitter. When GABA binds the GABAA receptor the channel opens and chloride enters the cell which makes it more resistant to depolarisation. Therefore,<unk>  has a depressant effect on synaptic transmission to reduce anxiety. The GABAA receptor is made up of 5 subunits out of a possible 19, and GABAA receptors made up of different combinations of subunits have different properties, different locations within the brain, and, importantly, different activities with regard to benzodiazepines.<unk>  and other triazolobenzodiazepines such as triazolam that have a triazole ring fused to their diazepine ring appear to have antidepressant properties. This is perhaps due to the similarities shared with tricyclic antidepressants, as they have two benzene rings fused to a diazepine ring.<unk>  causes a marked suppression of the hypothalamic–pituitary–adrenal axis. The therapeutic properties of<unk>  are similar to other benzodiazepines and include anxiolytic, anticonvulsant, muscle relaxant, hypnotic and amnesic; however, it is used mainly as an anxiolytic. Giving<unk> , as compared to lorazepam, has been demonstrated to elicit a statistically significant increase in extracellular dopamine D1 and D2 concentrations in the striatum. Pharmacokinetics<unk>  is metabolized into 4-hydroxyalprazolam (top) and α-hydroxyalprazolam (bottom).<unk>  is taken orally, and is absorbed well – 80% of<unk>  binds to proteins in the serum (the majority binding to albumin). The concentration of<unk>  peaks after one to two hours.<unk>  is metabolized in the liver, mostly by the enzyme cytochrome P450 3A4 (CYP3A4). Two major metabolites are produced: 4-hydroxyalprazolam and α-hydroxyalprazolam, as well as an inactive benzophenone. The low concentrations and low potencies of 4-hydroxyalprazolam and α-hydroxyalprazolam indicate that they have little to no contribution to the effects of<unk> . The metabolites, as well as some unmetabolized<unk> , are filtered out by the kidneys and are excreted in the urine.
Alprazolam
Loprazolam
Clotiazepam
Clonazepam
Phenazepam
Diclazepam
Medazepam
Pinazepam