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Alprazolam
Systematic (IUPAC) name
8-chloro-1-methyl-6-phenyl-4H- [1,2,4]triazolo[4,3-a][1,4]benzodiazepine Identifiers CAS number 28981-97-7 ATC code N05BA12 PubChem 2118 DrugBank APRD00280 Chemical data Formula C17H13ClN4 Mol. mass 308.765 Pharmacokinetic data Bioavailability 80-90% Metabolism Hepatic Half life 6-12 hours Excretion Renal Therapeutic considerations Pregnancy cat. D(US) Legal statusSchedule IV(US) Routes OralAlprazolam, also known under the trade names Xanax and Niravam, is a short-acting drug in the benzodiazepine class used to treat severe anxiety disorders and as an adjunctive treatment for anxiety associated with clinical depression. Contents 1 History 2 Pharmacology 3 Pharmacokinetics 4 Indications 5 Availability 6 Packaging 7 Side effects 8 Physical dependence and withdrawal 9 Contraindications 9.1 Overdose 9.2 Pregnancy 9.2.1 Teratogenicity classification 9.2.2 Effects on the fetus 9.2.3 Labor and delivery 9.2.4 Nursing mothers (neonates) 9.3 Geriatric use 10 Food and drug interactions 11 Special precautions 12 Recreational use 12.1 Patients at a high risk for abuse and dependence 13 Legal status 14 References 15 External links // History"[The public often does] underestimate the extent to which certain disorders affect the general populace. When you treat them, it can make a tremendous amount of difference in their lives." (David Sheehan, first discovered alprazolam's efficacy in treating panic disorder.[1]) Alprazolam was first synthesized by Upjohn (now a part of Pfizer). Its patent (#3,987,052)[2] was filed on October 29, 1969, granted on October 19, 1976 and expired in September 1993. It was released in 1983 to international market and its use began around 1990 in Europe. The first indication for which alprazolam was approved was panic disorder. Upjohn took this direction at the behest of a young psychiatrist David Sheehan. Sheehan's suggestion was to use the confusion DSM-III created in the classification of anxiety disorders (a distinction had just been made in DSM-III between generalized anxiety disorder (GAD) and panic disorder). Panic disorder was, at that point, perceived to be rare and treatable only with tricyclic antidepressants; benzodiazepines were thought to be ineffective. However, from his clinical experience, Sheehan knew panic disorder to be both widespread among the populace and well responding to benzodiazepines. He suggested to Upjohn that marketing alprazolam for panic disorder will both cover new diagnostic territory and stress the unique potency of this drug. Sheehan describes that the first group of patients treated by alprazolam was so impressed by its action that they knew outright—this drug was going to be a hit. A few of them pooled their money and bought the Upjohn’s stock. Several months later, when alprazolam was approved by the FDA, they sold out and made a profit.[3] PharmacologyAlprazolam is a triazolobenzodiazepine[4], that is, a benzodiazepine with a triazolo-ring attached to its structure. Benzodiazepines produce a variety of effects by modulating the GABAA subtype of the GABA receptor, the most prolific inhibitory receptor within the brain. The GABAA receptor is made up from 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 in regards to benzodiazepines. In order for GABAA receptors to be sensitive to the action of benzodiazepines they need to contain an α and a γ subunit, where the benzodiazepine binds. Once bound, the benzodiazepine locks the GABAA receptor into a conformation where the neurotransmitter GABA has much higher affinity for the GABAA receptor, increasing the frequency of opening of the associated Chloride ion channel and hyperpolarising t |