Giving alprazolam, as compared to lorazepam, has been demonstrated to elicit a statistically significant increase in extracellular dopamine D1 and D2 concentrations in the striatum. Pharmacokinetics
Alprazolam is taken orally, and is absorbed well – 80% of alprazolam binds to proteins in the serum (the majority binding to albumin). The concentration of alprazolam peaks after one to two hours.Alprazolam 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 alprazolam.The metabolites, as well as some unmetabolized alprazolam, are filtered out by the kidneys and are excreted in the urine. Chemistry
Physical properties
Alprazolam is a triazole and benzodiazepine derivative substituted with a phenyl group at position 6, with a chlorine atom at position 8 and with a methyl group at position 1. It is an analogue of triazolam, the difference between them being the absence of a chlorine atom in the ortho position of the phenyl ring. It is slightly soluble in chloroform, soluble in alcohol, slightly soluble in acetone and insoluble in water. It has a melting point of 228–229.5 °C (442.4–445.1 °F; 501.1–502.6 K). Synthesis
For the synthesis of alprazolam the same method can be used as for triazolam, excepting that it starts from 2-amino-5-chlorobenzophenone. However, an alternative easier synthesis starting with 2,6-dichloro-4-phenylquinoline has been suggested, in which it reacts with hydrazine giving 6-chloro-2-hydrazino-4-phenylquinoline.
The FDA label advises that the physician should periodically reassess the usefulness of the drug. Panic disorder
Alprazolam is effective in the relief of moderate to severe anxiety and panic attacks. However, it is not a first-line treatment since the development of selective serotonin reuptake inhibitors. Alprazolam is not recommended in Australia for the treatment of panic disorder because of concerns regarding tolerance, dependence, and abuse. Most evidence shows that the benefits of alprazolam in treating panic disorder last only four to ten weeks. However, people with panic disorder have been treated on an open basis for up to eight months without apparent loss of benefit.Alprazolam is recommended by the World Federation of Societies of Biological Psychiatry (WFSBP) for treatment-resistant cases of panic disorder where there is no history of tolerance or dependence. Anxiety disorders
Anxiety associated with depression is responsive to alprazolam. Clinical studies have shown that the effectiveness is limited to 4 months for anxiety disorders. However, the research into antidepressant properties of alprazolam is poor and has only assessed its short-term effects against depression. In one study, some long term, high-dosage users of alprazolam developed reversible depression. In the US, alprazolam is FDA-approved for the management of anxiety disorders (a condition corresponding most closely to the APA Diagnostic and Statistical Manual DSM-IV-TR diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. In the UK, alprazolam is recommended for the short-term treatment (2–4 weeks) of severe acute anxiety.