Alprazolam

Effects

AnxiolyticSedativeMuscle RelaxantAmnesiaDystaxiaHiccupsLoss of timeLoss of motor skills TS

Overview

Alprazolam (also known as Xanax) is a depressant substance of the benzodiazepine class. Its characteristic effects include anxiety suppression, sedation, disinhibition, and muscle relaxation.[1] PW

An extremely common benzodiazepine better known as Xanax, frequently prescribed for the treatment of anxiety and panic disorders. Alprazolam is short-lasting and primarily anxiolytic, though also possesses hypnotic properties. At high doses amnesia and loss of inhibition are common. Do not mix with other depressants.[2–7] TS

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. Alprazolam is most commonly prescribed in the management of anxiety disorders, especially panic disorder and generalized anxiety disorder (GAD). Other uses include the treatment of chemotherapy-induced nausea, together with other treatments. Alprazolam is generally taken orally.[8][9][10] WP

Common side effects include sleepiness, depression, suppressed emotions, mild to severe decreases in motor skills, hiccups, dulling or declining of cognition, decreased alertness, dry mouth (mildly), decreased heart rate, impairment of judgment (usually in higher than therapeutic doses), and decreased memory formation, depending on dosage. Some of the sedation and drowsiness may improve within a few days.[10][11][12] WP

Benzodiazepine withdrawal symptoms may occur if use is suddenly decreased.[10][13] WP

Alprazolam was developed by Jackson Hester Jr. at the Upjohn Company and patented in 1971 and approved for medical use in the United States in 1981. Alprazolam is a Schedule IV controlled substance and is a common drug of abuse. It is available as a generic medication. In 2023, it was the 37th most commonly prescribed medication in the United States, with more than 15 million prescriptions.[9][10][14–19] WP

History

In popular culture

• Take Your Pills: Xanax, a 2022 Netflix documentary, provides an overview of the drug's history and usage.[23][24] WP

Legal status

• Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.[25] PW
• Australia: Alprazolam was originally a Schedule 4 (prescription only) medication; however, as of January 2014, it will become a Schedule 8 medication, subjecting it to more rigorous prescribing requirements.[26] PW
• Austria: Alprazolam is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich). PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Czechia: Alprazolam is a Schedule IV (List 7) substance. Sold exclusively with a prescription "without a blue stripe" (§ 1, g), 1. of Nařízení vlády č. 463/2013 Sb.)[27][28] PW
• France: Alprazolam is a List I substance and is available for prescription. It is illegal to buy without a prescription.[29] PW
• Germany: Alprazolam is controlled under Anlage III BtMG (Narcotics Act, Schedule III) as of August 1, 1986. It can only be prescribed on a narcotic prescription form, except preparations which contain up to 1 mg alprazolam in each dosage form.[30][31] PW
• Ireland: Alprazolam is a Schedule 4 medicine.[32] PW
• Italy: Alprazolam is a schedule IV drug (Tabella 4) of the "Testo unico sulla droga (D.P.R. 309/90)". When prescribed for medical use it falls under Pharmaceuticals section B and E (Tabella medicinali sezione B ed E).[33][34] PW
• Russia: In Russia, since 2013, alprazolam is a Schedule III controlled substance.[35] PW
• Sweden: Alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).[36] PW
• Switzerland: Alprazolam is a controlled substance specifically named under Verzeichnis B. Medicinal use is permitted.[37] PW
• Turkey: Alprazolam is a 'green prescription' only substance and illegal when sold or possessed without a prescription.[38] PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• The Netherlands: Alprazolam is a List 2 substance of the Opium Law and is available for prescription.[39] PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• United Kingdom: Alprazolam is classified as a controlled drug and listed under Schedule IV, Part I (CD Benz POM) of the Misuse of Drugs Regulations 2001, allowing possession with a valid prescription. The Misuse of Drugs Act 1971 makes it illegal to possess the drug without a prescription and, for such purposes, it is classified as a Class C drug.[40] PW
• United States: Alprazolam is a prescription medication assigned to Schedule IV of the Controlled Substances Act by the DEA.[41] PW

Legal status

Alprazolam has varied legal status depending on jurisdiction: WP

• In the United States, alprazolam is a prescription drug and is assigned to Schedule IV of the Controlled Substances Act by the Drug Enforcement Administration (DEA).[42] WP
• Under the UK drug misuse classification system, alprazolam is a Class C drug. In the UK, alprazolam is not available on the National Health Service (NHS) and can only be obtained on a private prescription.[43][44][45] WP
• In Ireland, alprazolam is a Schedule 4 medicine.[46] WP
• In Sweden, alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).[36] WP
• In the Netherlands, alprazolam is a List 2 substance of the Opium Law and is available for prescription. WP⚠ Wikipedia itself has flagged this text: citation needed.
• In Germany, alprazolam can be prescribed normally in doses up to 1 mg. Higher doses are scheduled as Anlage III narcotic drugs and require a special prescription form.[31] WP
• In Australia, alprazolam, as of February 2014, is a Schedule 8 medication.[26][47][48] WP
• In the Philippines, alprazolam is legally classified as a "dangerous drug" under the Comprehensive Dangerous Drugs Act of 2002, along with other schedule drugs listed in the 1971 Convention on Psychotropic Substances. The importation of dangerous drugs including alprazolam, requires authorization from the Philippine Drug Enforcement Agency.[49][50] WP

Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.[51] WP

Pharmacology

Pharmacology

Alprazolam is a GABAA receptor positive allosteric modulator. 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, and anticonvulsant activity. The activity of alprazolam in the central nervous system is dose-dependent.[9][52] WP

Mechanism of action

Alprazolam is classed as a high-potency triazolobenzodiazepine: a benzodiazepine with a triazole ring attached to its structure. As a benzodiazepine, alprazolam 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 the inhibitory or calming effects of alprazolam on the nervous system. The binding of alprazolam 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, alprazolam has a depressant effect on synaptic transmission to reduce anxiety.[52–55] WP

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. Alprazolam 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. Alprazolam causes a marked suppression of the hypothalamic–pituitary–adrenal axis. The therapeutic properties of alprazolam are similar to other benzodiazepines and include anxiolytic, anticonvulsant, muscle relaxant, hypnotic, and amnesic; however, it is used mainly as an anxiolytic.[56–59] WP

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.[60][61] WP

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.[9] WP

Alprazolam is metabolized in the liver, mostly by the cytochrome enzyme 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.[9] WP

The metabolites and some unmetabolized alprazolam are filtered out by the kidneys and are excreted in the urine.[9] WP

Detection

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.[62] WP

Chemistry

Formula

C17H13ClN4 PC

CAS number

28981-97-7 PC

Molar mass (g/mol)

308.8 PC

IUPAC name (computed by PubChem)

8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine PC

SMILES

CC1=NN=C2N1C3=C(C=C(C=C3)Cl)C(=NC2)C4=CC=CC=C4 PC

InChIKey

VREFGVBLTWBCJP-UHFFFAOYSA-N PC

PubChem CID

2118

Pop culture

No references added yet.

References

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