Alprazolam

Identification

Summary

Alprazolam is a triazolobenzodiazepine with intermediate onset commonly used to treat panic disorders and generalized anxiety in addition to anxiety associated with depression.

Brand Names
Niravam, Xanax
Generic Name
Alprazolam
DrugBank Accession Number
DB00404
Background

Alprazolam is a triazolobenzodiazepine indicated for the treatment of anxiety and panic disorders.18,19 It is mainly metabolized by CYP3As and so is contraindicated with CYP3A inhibitors like ketoconazole and itraconazole.18,19 Benzodiazepine treatment should be stopped gradually by tapering down a patient's dose to avoid withdrawal symptoms.4 Alprazolam's adverse effects are generally related to the sedation it can cause.4 Alprazolam has been mixed with alcohol as a drug of abuse to potentiate the sedative effects of the drug which may lead to coma and death.4 Alprazolam was given FDA approval on October 16, 1981.14

Type
Small Molecule
Groups
Approved, Illicit, Investigational
Structure
Thumb
Weight
Average: 308.765
Monoisotopic: 308.082874143
Chemical Formula
C17H13ClN4
Synonyms
  • 8-Chloro-1-methyl-6-phenyl-4H-s-triazolo(4,3-a)(1,4)benzodiazepine
  • Alprazolam
External IDs
  • AZ-002
  • TUS-1
  • U 31,889
  • U-31,889
  • U-31889

Pharmacology

Indication

Alprazolam is indicated for the acute treatment of generalized anxiety disorder in adults.18 Alprazolam is also indicated, either as a standard or extended-release formulation, for the treatment of panic disorder with or without agoraphobia in adults.18,19

Alprazolam may also be prescribed off-label for insomnia, premenstrual syndrome, and depression.3

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
Pharmacodynamics

Alprazolam is a benzodiazepine that binds γ-aminobutyric acid (GABA) type-A receptors (GABAARs) to enhance their inhibitory effect on neurotransmission, specifically in the brain.18,19 Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death; patients taking benzodiazepines and opioids concurrently may require lower doses of one or both medications, depending on their clinical situation. Patients with pre-existing impaired respiratory function are at increased risk of adverse effects including death during treatment with benzodiazepines. In addition, due to its CNS depressant effects, patients taking alprazolam should avoid operating heavy machinery or driving and should avoid other CNS depressants such as alcohol. As with other benzodiazepines, alprazolam carries a risk of abuse, misuse, and addiction, which is higher in predisposed individuals and may require strict monitoring. Cessation of therapy may result in acute or protracted withdrawal symptoms, which may be life-threatening; the patient dose should be gradually tapered whenever discontinuation or reduced dosage are necessary. Newborns born to mothers using alprazolam later in pregnancy may suffer from sedation and withdrawal symptoms. As CYP3A is required for the initial step in alprazolam metabolism, alprazolam is contraindicated in patients taking strong CYP3A inhibitors, such as ketoconazole and itraconazole; milder CYP3A inhibitors still necessitate alprazolam dosage adjustments. Lastly, benzodiazepines may have negative effects, such as panic disorders, increased suicide incidence, and episodes of mania/hypomania, in patients suffering from depression.4,7,18,19

Mechanism of action

Neurotransmission relies on excitatory and inhibitory signalling. γ-aminobutyric acid (GABA) type-A receptors (GABAARs) are members of the pentameric ligand-gated ion channel (PLGIC) superfamily located synaptically and perisynaptically to mediate phasic inhibition and extrasynaptically to mediate tonic inhibition. GABAARs comprise a variety of subunits from a homologous family whose members are named based on sequence identity as one of α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3. Each subunit possesses an extracellular (ECD), transmembrane (TMD), and intracellular (ICD) domain; inter-subunit interfaces are the primary points of neurotransmitter and modulator binding, described by coordination of the principal (+) and complementary (-) sites in each subunit. Binding of GABA to GABAARs induces pore opening, rapid flow of chloride ions, and synaptic hyperpolarization, which in turn manifests as an inhibitory signal.8,9

The most prevalent GABAARs in vivo are the α1β2γ2 receptors, which contain both GABA (β+/α-) and benzodiazepine (BZD, α+/γ-) binding sites in the intersubunit interfaces of the relevant subunits.8,9,10 In general, any receptors containing an αxz interface, where x = 1-3,5 and z = 1-3, have potential high-affinity BZD binding sites, although small sequence differences between subunits may alter binding affinity to individual molecules. The α4 and α6 subunits, in which an otherwise conserved histidine is replaced by arginine, do not bind traditional BZD ligands such as diazepam and hence are considered "diazepam-insensitive".8,9,10 GABA binding results in a series of conformational changes in the ECDs of GABAAR β subunits, "locking" each to its neighbouring α- interface. The binding of alprazolam in the high-affinity BZD site stabilizes the α+/γ- interface and facilitates the conformational changes that lead to pore opening, hence functioning as a positive allosteric modulator.11

The exact manner in which GABAAR allosteric modulation mediates the therapeutic and unwanted effects of benzodiazepines remains unclear.3,4 Earlier studies suggested that the primary factor was the α subunit composition, with α1-containing receptors mediating the sedative effects, α2/3-containing receptors the anxiolytic effects, and α5-containing receptors the memory effects of benzodiazepines.12 More recent studies suggest a more complex set of factors including subunit composition, physiological location, neuronal circuit, and nerve cell type.13 To further complicate matters, there may be up to five distinct BZD binding sites on GABAARs, with site 1 corresponding to the classical high-affinity α+/γ- interface. The effects of binding at sites 2-4 are not fully understood and likely impart greater complexity to benzodiazepine pharmacological action.9,10

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
AGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
Absorption

Alprazolam administered orally is rapidly absorbed in the gastrointestinal tract, reaching Cmax in about 1.8 (1-2) hours. Absorption is high, resulting in an oral bioavailability of 84-91%. A 1 mg oral dose results in a Cmax of 12-22 μg/L.2,18

The extended-release formulation of alprazolam (XANAX XR) has similar absorption, bioavailability, and pharmacokinetics as the standard release, with the exception that the Tmax is ~10 hours compared to 1-2 hours. Temporal dosing alters these parameters, with Cmax increasing by 30% and Tmax decreasing by one hour when dosed at night as opposed to in the morning.19

Food has an effect on alprazolam absorption; a high-fat meal up to two hours before dosing increases the Cmax by ~25% and either a reduction (food consumed immediately prior to dosing) or increase (food consumed after dosing) of ~1/3 in Tmax. Neither the AUC nor half-life are appreciably affected by eating.19

Volume of distribution

Alprazolam has a volume of distribution following oral administration of 0.8-1.3L/kg.2 Alprazolam crosses the blood-brain barrier.4

Protein binding

Alprazolam is ~80% protein-bound in serum.18,19 The majority of this protein binding is to serum albumin.1,18,19 Alprazolam is also bound to alpha1-acid glycoprotein with low frequency.2

Metabolism

Alprazolam is metabolized to less effective metabolites by various CYPs including CYP3A4, CYP3A5, CYP3A7, and CYP2C9.5,6,16,18,19 The majority of alprazolam metabolism is mediated by hydroxylation via CYP3As.5,6,2,16,18,19 4-hydroxyalprazolam has 20% the binding affinity of the parent drug, alpha-hydroxyalprazolam has 66% the affinity, and the benzophenone metabolite has <1% the affinity.2,18,19

Hover over products below to view reaction partners

Route of elimination

Alprazolam is mainly eliminated in the urine.18,19 A large portion of the dose is eliminated as unmetabolized alprazolam.2 <10% of the dose is eliminated as alpha-hydroxy-alprazolam and 4-hydroxy-alprazolam.2

Half-life

Alprazolam has a mean plasma elimination half-life of 11.2 hours in healthy patients (range 6.3-26.9 hours).18 The mean half-life is 16.3 hours (range 9.0-26.9 hours) in the elderly, 21.8 hours (range 9.9-40.4 hours) in obese patients, and 19.7 hours (range 5.8-65.3 hours) in patients with alcoholic liver disease.18 The half-life is 25% higher in Asian patients compared to Caucasians.18 Other studies have shown the half-life to be 9-16h.2 The extended-release formulation has a half-life of 10.7-15.8 hours in healthy adult patients.19

Clearance

A 0.8 mg oral dose of alprazolam had a clearance of 0.90 ± 0.21 mL/min/kg, which increased to 2.13 ± 0.54 mL/min/kg when coadministered with the strong CYP3A4 inducer carbamazepine.18,19 Other studies have demonstrated a clearance of 0.70-1.5mL/min/kg.2

Adverse Effects
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
Toxicity

Alprazolam overdose can present as sleepiness, confusion, poor coordination, slow reflexes, coma, and death.18,19 Taking alprazolam with alcohol lowers the threshold for overdose.18,19 Patients should have their respiration, pulse, and blood pressure monitored.18,19 Patients can be treated by gastric lavage and intravenous fluids.18,19. If hypotension occurs, patients may be treated with vasopressors.18,19 In known, or suspected overdoses, patients can be given the benzodiazepine receptor antagonist flumazenil in addition to other methods of management.18,19

Oral LD50 in rats is 331-2171mg/kg.Label

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Alprazolam is combined with 1,2-Benzodiazepine.
AbacavirAlprazolam may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Alprazolam can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Alprazolam can be increased when combined with Abatacept.
AbirateroneThe metabolism of Alprazolam can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Alprazolam can be decreased when combined with Acalabrutinib.
AceclofenacAceclofenac may decrease the excretion rate of Alprazolam which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Alprazolam which could result in a higher serum level.
AcetaminophenThe metabolism of Alprazolam can be decreased when combined with Acetaminophen.
AcetazolamideThe metabolism of Alprazolam can be decreased when combined with Acetazolamide.
Interactions
Improve patient outcomes
Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.
Learn more
Food Interactions
  • Avoid alcohol. Alcohol may potentiate the CNS depressant effects of this drug.
  • Avoid grapefruit products.
  • Limit caffeine intake.
  • Take with or without food. Food increases the Cmax of extended release alprazolam by 25%, but the AUC and half life are not affected.

Products

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
Product Images
International/Other Brands
Alplax / Alprazolan / Alpronax / Alprox / Alviz / Cassadan / Esparon / Ralozam / Restyl / Solanax / Staccato alprazolam (Alexza) / Tafil / Trankimazin / Tranquinal / Xanor
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AlprazolamTablet0.5 mgOralJamp Pharma CorporationNot applicableNot applicableCanada flag
AlprazolamTablet, extended release1 mg/1OralZydus Pharmaceuticals Usa, Inc.2008-10-28Not applicableUS flag
AlprazolamTablet0.25 mgOralSanis Health Inc2010-04-30Not applicableCanada flag
AlprazolamTablet2 mgOralJamp Pharma CorporationNot applicableNot applicableCanada flag
AlprazolamTablet, extended release3 mg/1OralZydus Pharmaceuticals Usa, Inc.2008-10-28Not applicableUS flag
AlprazolamTablet0.25 mgOralJamp Pharma CorporationNot applicableNot applicableCanada flag
AlprazolamTablet, extended release0.5 mg/1OralZydus Pharmaceuticals Usa, Inc.2008-10-28Not applicableUS flag
AlprazolamTablet1 mgOralPro Doc Limitee2004-04-01Not applicableCanada flag
AlprazolamTablet1 mgOralJamp Pharma CorporationNot applicableNot applicableCanada flag
AlprazolamTablet, extended release2 mg/1OralZydus Pharmaceuticals Usa, Inc.2008-10-28Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AlprazolamTablet1 mg/1OralLake Erie Medical DBA Quality Care Products LLC2017-01-272019-10-11US flag
AlprazolamTablet0.5 mg/1OralContract Pharmacy Services Pa1981-10-16Not applicableUS flag
AlprazolamTablet0.25 mg/1OralKAISER FOUNDATION HOSPITALS2008-07-142017-04-30US flag
AlprazolamTablet, extended release1 mg/1OralRebel Distributors2009-12-03Not applicableUS flag
AlprazolamTablet2 mg/1OralRpk Pharmaceuticals, Inc.1981-10-16Not applicableUS flag
AlprazolamTablet.25 mg/1OralNCS HealthCare of KY, Inc dba Vangard Labs1995-12-292020-02-29US flag
AlprazolamTablet1 mg/1OralDirect Rx2021-05-27Not applicableUS flag
AlprazolamTablet, extended release3 mg/1OralTeva2007-06-042009-02-28US flag
AlprazolamTablet0.25 mg/1OralBreckenridge Pharmaceutical, Inc.2018-07-09Not applicableUS flag
AlprazolamTablet0.25 mg/1OralUnit Dose Services1995-12-292017-12-31US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
GabazolamineAlprazolam (0.25 mg/1) + Choline (125 mg/1)KitOralPhysician Therapeutics Llc2011-07-07Not applicableUS flag
Gabazolamine-0.5Alprazolam (0.5 mg/1) + Choline (125 mg/1)KitOralPhysician Therapeutics Llc2011-07-07Not applicableUS flag
Sentrazolam AMAlprazolam (0.25 mg/1) + Choline (250 mg/1)KitOralPhysician Therapeutics Llc2011-07-07Not applicableUS flag

Categories

ATC Codes
N05BA12 — Alprazolam
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 1,2,4-triazolo[4,3-a][1,4]benzodiazepines. These are aromatic compounds containing a 1,4-benzodiazepine fused to and sharing a nitrogen atom with a 1,2,4-triazole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
1,4-benzodiazepines
Direct Parent
1,2,4-triazolo[4,3-a][1,4]benzodiazepines
Alternative Parents
Benzene and substituted derivatives / Aryl chlorides / Triazoles / Heteroaromatic compounds / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
1,2,4-triazole / 1,2,4-triazolo[4,3-a][1,4]benzodiazepine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Benzenoid / Heteroaromatic compound / Hydrocarbon derivative
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, triazolobenzodiazepine (CHEBI:2611)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
YU55MQ3IZY
CAS number
28981-97-7
InChI Key
VREFGVBLTWBCJP-UHFFFAOYSA-N
InChI
InChI=1S/C17H13ClN4/c1-11-20-21-16-10-19-17(12-5-3-2-4-6-12)14-9-13(18)7-8-15(14)22(11)16/h2-9H,10H2,1H3
IUPAC Name
12-chloro-3-methyl-9-phenyl-2,4,5,8-tetraazatricyclo[8.4.0.0²,⁶]tetradeca-1(10),3,5,8,11,13-hexaene
SMILES
CC1=NN=C2CN=C(C3=CC=CC=C3)C3=C(C=CC(Cl)=C3)N12

References

Synthesis Reference

Hester, J.B., Jr.; US. Patent 3,681,343; August 1,1972; assigned to The Upjohn Company. Hester, J.B., Jr.; US.Patent 3,781,289; December 25,1973;assigned to The Upjohn Company. Hester, J.B., Jr.; U S . Patent 3,709898; January 9,1973; assigned to The Upjohn Company.

General References
  1. Dangkoob F, Housaindokht MR, Asoodeh A, Rajabi O, Rouhbakhsh Zaeri Z, Verdian Doghaei A: Spectroscopic and molecular modeling study on the separate and simultaneous bindings of alprazolam and fluoxetine hydrochloride to human serum albumin (HSA): with the aim of the drug interactions probing. Spectrochim Acta A Mol Biomol Spectrosc. 2015 Feb 25;137:1106-19. doi: 10.1016/j.saa.2014.08.149. Epub 2014 Oct 7. [Article]
  2. Greenblatt DJ, Wright CE: Clinical pharmacokinetics of alprazolam. Therapeutic implications. Clin Pharmacokinet. 1993 Jun;24(6):453-71. doi: 10.2165/00003088-199324060-00003. [Article]
  3. George TT, Tripp J: Alprazolam . [Article]
  4. Verster JC, Volkerts ER: Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam: a review of the literature. CNS Drug Rev. 2004 Spring;10(1):45-76. [Article]
  5. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  6. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. [Article]
  7. Ait-Daoud N, Hamby AS, Sharma S, Blevins D: A Review of Alprazolam Use, Misuse, and Withdrawal. J Addict Med. 2018 Jan/Feb;12(1):4-10. doi: 10.1097/ADM.0000000000000350. [Article]
  8. Scott S, Aricescu AR: A structural perspective on GABAA receptor pharmacology. Curr Opin Struct Biol. 2019 Feb;54:189-197. doi: 10.1016/j.sbi.2019.03.023. Epub 2019 May 23. [Article]
  9. Olsen RW: GABAA receptor: Positive and negative allosteric modulators. Neuropharmacology. 2018 Jul 1;136(Pt A):10-22. doi: 10.1016/j.neuropharm.2018.01.036. Epub 2018 Jan 31. [Article]
  10. Sigel E, Ernst M: The Benzodiazepine Binding Sites of GABAA Receptors. Trends Pharmacol Sci. 2018 Jul;39(7):659-671. doi: 10.1016/j.tips.2018.03.006. Epub 2018 Apr 30. [Article]
  11. Masiulis S, Desai R, Uchanski T, Serna Martin I, Laverty D, Karia D, Malinauskas T, Zivanov J, Pardon E, Kotecha A, Steyaert J, Miller KW, Aricescu AR: GABAA receptor signalling mechanisms revealed by structural pharmacology. Nature. 2019 Jan;565(7740):454-459. doi: 10.1038/s41586-018-0832-5. Epub 2019 Jan 2. [Article]
  12. Rowlett JK, Platt DM, Lelas S, Atack JR, Dawson GR: Different GABAA receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates. Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):915-20. doi: 10.1073/pnas.0405621102. Epub 2005 Jan 11. [Article]
  13. Engin E, Benham RS, Rudolph U: An Emerging Circuit Pharmacology of GABAA Receptors. Trends Pharmacol Sci. 2018 Aug;39(8):710-732. doi: 10.1016/j.tips.2018.04.003. Epub 2018 Jun 11. [Article]
  14. FDA Approved Drug Products: Xanax [Link]
  15. FDA Pregnancy Categories [Link]
  16. Flockhart Table of Drug Interactions [Link]
  17. FDA Approved Drug Products: XANAX (Alprazolam) tablets [Link]
  18. FDA Approved Drug Products: XANAX (alprazolam) tablets [Link]
  19. FDA Approved Drug Products: XANAX XR (alprazolam) extended-release tablets [Link]
Human Metabolome Database
HMDB0014548
KEGG Drug
D00225
KEGG Compound
C06817
PubChem Compound
2118
PubChem Substance
46507078
ChemSpider
2034
BindingDB
50001728
RxNav
596
ChEBI
2611
ChEMBL
CHEMBL661
ZINC
ZINC000000000903
Therapeutic Targets Database
DAP000239
PharmGKB
PA448333
PDBe Ligand
08H
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Alprazolam
PDB Entries
3u5j / 6huo
FDA label
Download (381 KB)
MSDS
Download (47.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceDriving Behavior1
4CompletedBasic ScienceHealthy Volunteers1
4CompletedDiagnosticAnxiety Disorders1
4CompletedOtherPsychomotor Impairment1
4CompletedTreatmentAnxiety2
4CompletedTreatmentGeneralized Anxiety Disorder (GAD)1
4CompletedTreatmentGeneralized Anxiety Disorder (GAD) / Panic Disorder1
4CompletedTreatmentInferior Alveolar Nerve Block Failure1
4CompletedTreatmentPanic Disorder2
4Not Yet RecruitingTreatmentAgitation on Recovery From Sedation1

Pharmacoeconomics

Manufacturers
  • Roxane laboratories inc
  • Actavis elizabeth llc
  • Amneal pharmaceuticals ny llc
  • Apotex inc
  • Barr laboratories inc
  • Corepharma llc
  • Impax laboratories inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Vintage pharmaceuticals llc
  • Watson laboratories inc florida
  • Zydus pharmaceuticals usa inc
  • Pharmacia and upjohn
  • Par pharmaceutical inc
  • Schwarz pharma inc
  • Alphapharm party ltd
  • Dava international inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Sun pharma global inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Pharmacia and upjohn co
Packagers
  • Actavis Group
  • Aidarex Pharmacuticals LLC
  • Alphapharm Party Ltd.
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • AzurPharma Inc.
  • Barr Pharmaceuticals
  • Bryant Ranch Prepack
  • Cardinal Health
  • Caremark LLC
  • Centaur Pharmaceuticals Pvt Ltd.
  • Cima Laboratories Inc.
  • Corepharma LLC
  • DAVA Pharmaceuticals
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Emcure Pharmaceuticals Ltd.
  • Eon Labs
  • Global Pharmaceuticals
  • Greenstone LLC
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Medisca Inc.
  • Medvantx Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Pharmacia Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepak Systems Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Rising Pharmaceuticals
  • Roxane Labs
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Sun Pharmaceutical Industries Ltd.
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Ultratab Labs Inc.
  • Va Cmop Dallas
  • Vintage Pharmaceuticals Inc.
  • Zydus Pharmaceuticals
Dosage Forms
FormRouteStrength
TabletSublingual0.5 mg
TabletOral2 mg
Tablet
Solution, concentrateOral1 mg/1mL
TabletOral
TabletOral.25 mg/1
TabletOral.5 mg/1
TabletOral0.25 mg/1
TabletOral0.5 mg/1
TabletOral0.50 mg
TabletOral1 mg/1
TabletOral1.00 mg/1
TabletOral2 mg/1
TabletOral2.00 mg/1
Tablet, extended releaseOral0.5 mg/1
Tablet, extended releaseOral1 mg/1
Tablet, extended releaseOral2 mg/1
Tablet, extended releaseOral3 mg/1
TabletOral1 mg
Tablet0.5 MG
Tablet0.25 MG
Tablet1.0 MG
Tablet, extended releaseOral2 mg
Solution / dropsOral
Tablet1 mg
SolutionOral1 mg
TabletOral0.5 mg
Tablet, orally disintegratingOral0.25 mg/1
Tablet, orally disintegratingOral0.5 mg/1
Tablet, orally disintegratingOral1 mg/1
Tablet, orally disintegratingOral2 mg/1
TabletOral0.25 mg
TabletOral.25 mg
TabletOral.5 mg
TabletOral0.25 mg / tab
TabletOral0.5 mg / tab
KitOral
TabletOral0.125 mg
Capsule
SolutionOral0.75 mg
TabletSublingual
Tablet, extended releaseOral0.5 mg
Tablet, extended releaseOral
TabletSublingual1 mg
Prices
Unit descriptionCostUnit
ALPRAZolam Intensol 1 mg/ml Concentrate 30ml Bottle67.03USD bottle
Niravam 2 mg Dispersible Tablet8.53USD dispersible tablet
Xanax xr 3 mg tablet7.25USD tablet
Xanax XR 3 mg 24 Hour tablet7.1USD tablet
Niravam 2 mg tablet6.86USD tablet
Niravam 1 mg Dispersible Tablet5.42USD dispersible tablet
Xanax xr 2 mg tablet4.84USD tablet
Xanax XR 2 mg 24 Hour tablet4.73USD tablet
Niravam 0.5 mg Dispersible Tablet4.2USD dispersible tablet
Niravam 1 mg tablet4.04USD tablet
Xanax 2 mg tablet3.82USD tablet
ALPRAZolam 3 mg 24 Hour tablet3.67USD tablet
Xanax XR 1 mg 24 Hour tablet3.64USD tablet
Xanax xr 1 mg tablet3.64USD tablet
Niravam 0.25 mg Dispersible Tablet3.45USD dispersible tablet
Niravam 0.5 mg tablet3.02USD tablet
Xanax XR 0.5 mg 24 Hour tablet3.01USD tablet
Xanax xr 0.5 mg tablet2.93USD tablet
ALPRAZolam 2 mg 24 Hour tablet2.53USD tablet
Niravam 0.25 mg tablet2.43USD tablet
ALPRAZolam 1 mg 24 Hour tablet2.33USD tablet
Xanax 1 mg tablet2.29USD tablet
Alprazolam 1 mg/ml oral conc2.23USD ml
Xanax 0.5 mg tablet1.3USD tablet
Alprazolam 2 mg tablet1.22USD tablet
Xanax 0.25 mg tablet1.09USD tablet
ALPRAZolam 0.5 mg 24 Hour tablet1.07USD tablet
Alprazolam 1 mg tablet0.78USD tablet
Alprazolam 0.5 mg tablet0.67USD tablet
Alprazolam 0.25 mg tablet0.55USD tablet
Apo-Alpraz 0.5 mg Tablet0.1USD tablet
Mylan-Alprazolam 0.5 mg Tablet0.1USD tablet
Novo-Alprazol 0.5 mg Tablet0.1USD tablet
Apo-Alpraz 0.25 mg Tablet0.08USD tablet
Mylan-Alprazolam 0.25 mg Tablet0.08USD tablet
Novo-Alprazol 0.25 mg Tablet0.08USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6221392No2001-04-242018-04-09US flag
US6024981No2000-02-152018-04-09US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)228-229.5 °CHester, J.B., Jr.; US. Patent3,681,343; August 1,1972; assigned to The Upjohn Company. Hester, J.B., Jr.; US.Patent3,781,289; December 25,1973;assigned to The Upjohn Company. Hester, J.B., Jr.; U S . Patent 3,709898; January 9,1973; assigned t o The Upjohn Company.
Predicted Properties
PropertyValueSource
Water Solubility0.0324 mg/mLALOGPS
logP2.23ALOGPS
logP2.37ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)18.3ChemAxon
pKa (Strongest Basic)5.08ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area43.07 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity98.88 m3·mol-1ChemAxon
Polarizability32.22 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9794
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.5099
P-glycoprotein inhibitor INon-inhibitor0.7301
P-glycoprotein inhibitor IIInhibitor0.8354
Renal organic cation transporterInhibitor0.7688
CYP450 2C9 substrateNon-substrate0.7907
CYP450 2D6 substrateNon-substrate0.9164
CYP450 3A4 substrateSubstrate0.7353
CYP450 1A2 substrateInhibitor0.8758
CYP450 2C9 inhibitorInhibitor0.8076
CYP450 2D6 inhibitorNon-inhibitor0.8137
CYP450 2C19 inhibitorInhibitor0.6519
CYP450 3A4 inhibitorNon-inhibitor0.6308
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8913
Ames testNon AMES toxic0.8957
CarcinogenicityNon-carcinogens0.6779
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3717 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.973
hERG inhibition (predictor II)Non-inhibitor0.8733
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0kdi-4792000000-9f1cdda14e36000955d3
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a59-0079000000-e4c35fb4df41aa5cc62e
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0bt9-0169000000-0e6779728f3bdec2acf1
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0910000000-9efa6a8a3dea17fc1ce7

Targets

Drugtargets
Accelerate your drug discovery research
with our fully connected ADMET & drug target dataset.
Learn more
Accelerate your drug discovery research with our ADMET & drug target dataset
Learn more
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [Article]
  2. Verster JC, Volkerts ER: Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam: a review of the literature. CNS Drug Rev. 2004 Spring;10(1):45-76. [Article]
  3. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
  4. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
Curator comments
Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
  2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. [Article]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  5. FDA Approved Drug Products: XANAX (Alprazolam) tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Allqvist A, Miura J, Bertilsson L, Mirghani RA: Inhibition of CYP3A4 and CYP3A5 catalyzed metabolism of alprazolam and quinine by ketoconazole as racemate and four different enantiomers. Eur J Clin Pharmacol. 2007 Feb;63(2):173-9. doi: 10.1007/s00228-006-0230-z. Epub 2007 Jan 3. [Article]
  2. Park JY, Kim KA, Park PW, Lee OJ, Kang DK, Shon JH, Liu KH, Shin JG: Effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy subjects. Clin Pharmacol Ther. 2006 Jun;79(6):590-9. doi: 10.1016/j.clpt.2006.02.008. [Article]
  3. Hirota N, Ito K, Iwatsubo T, Green CE, Tyson CA, Shimada N, Suzuki H, Sugiyama Y: In vitro/in vivo scaling of alprazolam metabolism by CYP3A4 and CYP3A5 in humans. Biopharm Drug Dispos. 2001 Mar;22(2):53-71. [Article]
  4. Flockhart Table of Drug Interactions [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Dangkoob F, Housaindokht MR, Asoodeh A, Rajabi O, Rouhbakhsh Zaeri Z, Verdian Doghaei A: Spectroscopic and molecular modeling study on the separate and simultaneous bindings of alprazolam and fluoxetine hydrochloride to human serum albumin (HSA): with the aim of the drug interactions probing. Spectrochim Acta A Mol Biomol Spectrosc. 2015 Feb 25;137:1106-19. doi: 10.1016/j.saa.2014.08.149. Epub 2014 Oct 7. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...

Components:
References
  1. Greenblatt DJ, Wright CE: Clinical pharmacokinetics of alprazolam. Therapeutic implications. Clin Pharmacokinet. 1993 Jun;24(6):453-71. doi: 10.2165/00003088-199324060-00003. [Article]

Drug created on June 13, 2005 13:24 / Updated on July 24, 2021 14:58