Alprazolam
Alprazolam, sold under the brand name Xanax among others, is a fast-acting, potent tranquilizer of moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines.[10] Alprazolam is most commonly used in management of anxiety disorders, specifically panic disorder or generalized anxiety disorder (GAD).[6] Other uses include the treatment of chemotherapy-induced nausea, together with other treatments.[9] GAD improvement occurs generally within a week.[11][12] Alprazolam is generally taken orally (by mouth).[9]
"Xanax" and "Xanny" redirect here. For the Billie Eilish song, see Xanny (song). For other uses, see Xanax (disambiguation).Clinical data
Xanax, Xanor, Niravam, others
- US DailyMed: Alprazolam
- AU: C[1]
Very high[2]
High[2]
- AU: S8 (Controlled drug)
- BR: Class B1 (Psychoactive drugs)
- CA: Schedule IV
- DE: Anlage III (Special prescription form required) (in doses higher than 1 mg)
- UK: POM (Prescription only) / Class C[4][5]
- US: WARNING[3]Schedule IV[6][7]
- UN: Psychotropic Schedule IV
- In general: ℞ (Prescription only)
80–90%
80%
Liver, via cytochrome P450 3A4
• Alpha-hydroxyalprazolam
• 4-hydroxyalprazolam
20~60 minutes[8]
Full release: 6 hours[8]
Extended release: 11.3 hours
C17H13ClN4
308.77 g·mol−1
Common side effects include sleepiness, depression or suppressed emotions, mild to severe decreases in motor skills, hiccups, dulling or declining of cognition as well as alertness or general awareness of one's surroundings or even behavior, dry mouth (mildly), decreased heart rate, suppression (physiological inhibition) of general central nervous system activity (opposite of physiological excitation), impairment of judgment (usually in higher than therapeutic doses), marginal to severe decreases in memory formation, decreased ability to process new information, as well as partial to complete amnesia (anterograde amnesia[13]) depending on dosage.[9] Some of the sedation and tiredness may improve within a few days.[14]
Alprazolam withdrawal may occur if use is suddenly decreased.[9][11]
Alprazolam was invented by Jackson Hester Jr. at the Upjohn Company[15] and patented in 1971 and approved for medical use in the United States in 1981.[9][16] Alprazolam is a Schedule IV controlled substance and is a common drug of abuse.[2][17] It is available as a generic medication.[6] In 2021, it was the 42nd most-commonly-prescribed medication in the United States, with more than 15 million prescriptions.[18][19]
Contraindications[edit]
Benzodiazepines require special precaution if used in children and in alcohol- or drug-dependent individuals. Particular care should be taken in pregnant or elderly people, people with substance use disorder history, particularly alcohol dependence, and people with comorbid psychiatric disorders.[25]
Alprazolam should be avoided or carefully monitored by medical professionals in individuals with myasthenia gravis, acute narrow-angle glaucoma, severe liver deficiencies such as cirrhosis, severe sleep apnea, pre-existing respiratory depression, marked neuromuscular respiratory, acute pulmonary insufficiency, chronic psychosis, hypersensitivity, allergy to alprazolam or other benzodiazepines, and borderline personality disorder, where it may induce suicidality and dyscontrol.[26][27][28]
Like all central nervous system depressants, alprazolam in larger-than-normal doses can cause significant deterioration in alertness and increase drowsiness, especially in those unaccustomed to the drug's effects.[29]
Chemistry[edit]
Physical properties[edit]
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.[88] It is slightly soluble in chloroform, soluble in alcohol, slightly soluble in acetone and insoluble in water.[89] It has a melting point of 228–229.5 °C (442.4–445.1 °F; 501.1–502.6 K).[89][90]
Synthesis[edit]
For the synthesis of alprazolam the same method can be used as for triazolam, excepting that it starts from 2-amino-5-chlorobenzophenone.[91] 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. Boiling the mixture with triethyl orthoacetate results in cyclization with the formation of the triazole ring. The product undergoes oxidative degradation in the presence of periodate and ruthenium dioxide in acetone solution, giving 2-[4-(3'-methyl-1,2,4-triazolo)]-5-chlorobenzophenone. Oxy-methylation with formaldehyde results in a product that is treated with phosphorus tribromide, when 2-[4-(3'-methyl-5'-bromomethyl-1,2,4-triazolo)]-5-chlorobenzophenone is obtained. By substituting the bromine atom with an amino group conferred by ammonia, it forms alprazolam triazolobenzophenone, following which an intermolecular heterocyclization takes place to obtain alprazolam.[88][92][90]
Detection[edit]
Quantification of alprazolam in blood and plasma samples may be necessary to confirm a diagnosis of intoxication in hospitalized patients, or to provide evidence in the case of crimes e.g., impaired driving arrest, or to assist in a thorough forensic investigation, e.g., in a medicolegal death investigation. Blood or plasma alprazolam concentrations are usually in a range of 10–100 μg/L in persons receiving the drug therapeutically, 100–300 μg/L in those arrested for impaired driving, and 300–2,000 μg/L in victims of acute overdosage. Most of the commercial immunoassays used for the benzodiazepine class of drugs cross-react with alprazolam, but confirmation and quantitative determination are usually done by chromatographic techniques.[93]
Forms of alprazolam[edit]
Alprazolam regular release and orally disintegrating tablets are available as 0.25 mg, 0.5 mg, 1 mg, and 2 mg tablets,[6] while extended release tablets are available as 0.5 mg, 1 mg, 2 mg, and 3 mg.[7] Liquid alprazolam is available in a 1 mg/mL oral concentrate. Inactive ingredients in alprazolam tablets and solutions include microcrystalline cellulose, corn starch, docusate sodium, povidone, sodium starch glycolate, lactose monohydrate, magnesium stearate, colloidal silicon dioxide, and sodium benzoate. In addition, the 0.25 mg tablet contains D&C Yellow No. 10 and the 0.5 mg tablet contains FD&C Yellow No. 6 and D&C Yellow No. 10.[6]
Society and culture[edit]
Patent[edit]
Alprazolam is covered under U.S. patent 3,987,052, which was filed in October 1969, granted in October 1976, and expired in September 1993.