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Identification
NameAlprazolam
Accession NumberDB00404  (APRD00280)
Typesmall molecule
Groupsapproved, illicit, investigational
Description

A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of panic disorders, with or without agoraphobia, and in generalized anxiety disorders. (From AMA Drug Evaluations Annual, 1994, p238)

Structure
Thumb
Synonyms
SynonymLanguageCode
AlprazolamNot AvailableJP16/USP/INN
SaltsNot Available
Brand names
NameCompany
AlplaxNot Available
AlprazolanNot Available
AlpronaxNot Available
AlproxNot Available
AlvizNot Available
CassadanNot Available
EsparonNot Available
NiravamNot Available
RalozamNot Available
RestylNot Available
SolanaxNot Available
TafilNot Available
TrankimazinNot Available
TranquinalNot Available
XanaxUpjohn
Xanax XRUpjohn
XanorNot Available
Brand mixturesNot Available
Categories
CAS number28981-97-7
WeightAverage: 308.765
Monoisotopic: 308.082874143
Chemical FormulaC17H13ClN4
InChI KeyVREFGVBLTWBCJP-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[8.4.0.0^{2,6}]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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzodiazepines
SubclassNot Available
Direct parentBenzodiazepines
Alternative parentsChlorobenzenes; Aryl Chlorides; Triazoles; Polyamines; Organochlorides
Substituentschlorobenzene; aryl halide; benzene; aryl chloride; 1,2,4-triazole; azole; polyamine; organochloride; organohalogen; organonitrogen compound
Classification descriptionThis compound belongs to the benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).
Pharmacology
IndicationFor the management of anxiety disorder or the short-term relief of symptoms of anxiety and for the treatment of panic disorder, with or without agoraphobia.
PharmacodynamicsAlprazolam, a benzodiazepine, is used to treat panic disorder and anxiety disorder. Unlike chlordiazepoxide, clorazepate, and prazepam, alprazolam has a shorter half-life and metabolites with minimal activity. Like other triazolo benzodiazepines such as triazolam, alprazolam may have significant drug interactions involving the hepatic cytochrome P-450 3A4 isoenzyme. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis. Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking.
Mechanism of actionBenzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.
AbsorptionReadily absorbed from the gastrointestinal tract. Bioavailability is 80-90%.
Volume of distributionNot Available
Protein binding80% (mainly to albumin)
Metabolism

Hepatic. Hydroxylated in the liver to α-hydroxyalprazolam, which is also active. This and other metabolites are later excreted in urine as glucuronides.

SubstrateEnzymesProduct
Alprazolam
alpha-HydroxyalprazolamDetails
Alprazolam
4-hydroxyalprazolamDetails
Route of eliminationAlprazolam and its metabolites are excreted primarily in the urine.
Half life6.3-26.9 hours
Clearance
  • 2.13 +/- 0.54 mL/min/kg [CYP3A inducers]
  • 0.90 +/- 0.21 mL/min/kg [without CYP3A inducers]
ToxicityOral, mouse: LD50=1020 mg/kg. Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9794
Caco-2 permeable + 0.8867
P-glycoprotein substrate Non-substrate 0.5099
P-glycoprotein inhibitor I Non-inhibitor 0.7301
P-glycoprotein inhibitor II Inhibitor 0.8354
Renal organic cation transporter Inhibitor 0.7688
CYP450 2C9 substrate Non-substrate 0.7907
CYP450 2D6 substrate Non-substrate 0.9164
CYP450 3A4 substrate Substrate 0.7353
CYP450 1A2 substrate Inhibitor 0.8758
CYP450 2C9 substrate Inhibitor 0.8076
CYP450 2D6 substrate Non-inhibitor 0.8137
CYP450 2C19 substrate Inhibitor 0.6519
CYP450 3A4 substrate Non-inhibitor 0.6308
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8913
Ames test Non AMES toxic 0.8957
Carcinogenicity Non-carcinogens 0.6779
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.3717 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.973
hERG inhibition (predictor II) Non-inhibitor 0.8733
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
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
ALPRAZolam Intensol 1 mg/ml Concentrate 30ml Bottle67.03USDbottle
Niravam 2 mg Dispersible Tablet8.53USDdispersible tablet
Xanax xr 3 mg tablet7.25USDtablet
Xanax XR 3 mg 24 Hour tablet7.1USDtablet
Niravam 2 mg tablet6.86USDtablet
Niravam 1 mg Dispersible Tablet5.42USDdispersible tablet
Xanax xr 2 mg tablet4.84USDtablet
Xanax XR 2 mg 24 Hour tablet4.73USDtablet
Niravam 0.5 mg Dispersible Tablet4.2USDdispersible tablet
Niravam 1 mg tablet4.04USDtablet
Xanax 2 mg tablet3.82USDtablet
ALPRAZolam 3 mg 24 Hour tablet3.67USDtablet
Xanax XR 1 mg 24 Hour tablet3.64USDtablet
Xanax xr 1 mg tablet3.64USDtablet
Niravam 0.25 mg Dispersible Tablet3.45USDdispersible tablet
Niravam 0.5 mg tablet3.02USDtablet
Xanax XR 0.5 mg 24 Hour tablet3.01USDtablet
Xanax xr 0.5 mg tablet2.93USDtablet
ALPRAZolam 2 mg 24 Hour tablet2.53USDtablet
Niravam 0.25 mg tablet2.43USDtablet
ALPRAZolam 1 mg 24 Hour tablet2.33USDtablet
Xanax 1 mg tablet2.29USDtablet
Alprazolam 1 mg/ml oral conc2.23USDml
Xanax 0.5 mg tablet1.3USDtablet
Alprazolam 2 mg tablet1.22USDtablet
Xanax 0.25 mg tablet1.09USDtablet
ALPRAZolam 0.5 mg 24 Hour tablet1.07USDtablet
Alprazolam 1 mg tablet0.78USDtablet
Alprazolam 0.5 mg tablet0.67USDtablet
Alprazolam 0.25 mg tablet0.55USDtablet
Apo-Alpraz 0.5 mg Tablet0.1USDtablet
Mylan-Alprazolam 0.5 mg Tablet0.1USDtablet
Novo-Alprazol 0.5 mg Tablet0.1USDtablet
Apo-Alpraz 0.25 mg Tablet0.08USDtablet
Mylan-Alprazolam 0.25 mg Tablet0.08USDtablet
Novo-Alprazol 0.25 mg Tablet0.08USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States60249811998-04-092018-04-09
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point228-229.5 °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.
water solubility40 mg/L at pH 7; 12 mg/mL at pH 1.2Not Available
logP2.12BIOBYTE (1995)
Predicted Properties
PropertyValueSource
water solubility3.24e-02 g/lALOGPS
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 area43.07ChemAxon
rotatable bond count1ChemAxon
refractivity98.88ChemAxon
polarizability32.22ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
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 Reference
  1. Risse SC, Whitters A, Burke J, Chen S, Scurfield RM, Raskind MA: Severe withdrawal symptoms after discontinuation of alprazolam in eight patients with combat-induced posttraumatic stress disorder. J Clin Psychiatry. 1990 May;51(5):206-9. Pubmed
  2. Wolf B, Griffiths RR: Physical dependence on benzodiazepines: differences within the class. Drug Alcohol Depend. 1991 Dec 31;29(2):153-6. Pubmed
  3. Haque W, Watson DJ, Bryant SG: Death following suspected alprazolam withdrawal seizures: a case report. Tex Med. 1990 Jan;86(1):44-7. Pubmed
  4. Hori A: Pharmacotherapy for personality disorders. Psychiatry Clin Neurosci. 1998 Feb;52(1):13-9. Pubmed
  5. Garcia-Algar O, Lopez-Vilchez MA, Martin I, Mur A, Pellegrini M, Pacifici R, Rossi S, Pichini S: Confirmation of gestational exposure to alprazolam by analysis of biological matrices in a newborn with neonatal sepsis. Clin Toxicol (Phila). 2007;45(3):295-8. Pubmed
External Links
ResourceLink
KEGG DrugD00225
KEGG CompoundC06817
PubChem Compound2118
PubChem Substance46507078
ChemSpider2034
ChEBI2611
ChEMBLCHEMBL661
Therapeutic Targets DatabaseDAP000239
PharmGKBPA448333
Drug Product Database2248706
RxListhttp://www.rxlist.com/cgi/generic/alpraz.htm
Drugs.comhttp://www.drugs.com/alprazolam.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/xan1491.shtml
WikipediaAlprazolam
ATC CodesN05BA12
AHFS Codes
  • 28:24.08
PDB EntriesNot Available
FDA labelshow(63.6 KB)
MSDSshow(47.3 KB)
Interactions
Drug Interactions
Drug
AmprenavirAmprenavir may increase the effect and toxicity of the benzodiazepine, alprazolam.
AprepitantAprepitant may increase the effect and toxicity of the benzodiazepine, alprazolam.
CarbamazepineCarbamazepine may decrease the effect of the benzodiazepine, alprazolam.
CimetidineCimetidine may increase the effect of the benzodiazepine, alprazolam.
ClarithromycinThe macrolide, clarithromycin, may increase the effect of the benzodiazepine, alprazolam.
ClozapineIncreased risk of toxicity
DelavirdineThe antiviral agent, delavirdine, may increase the effect and toxicity of the benzodiazepine, alprazolam.
DigoxinThe benzodiazepine, alprazolam, may increase the effect of digoxin.
EfavirenzThe antiviral agent, efavirenz, may increase the effect and toxicity of the benzodiazepine, alprazolam.
ErythromycinThe macrolide, erythromycin, may increase the effect of the benzodiazepine, alprazolam.
EthotoinEthotoin may increase the metabolism of alprazolam via CYP3A4.
FluconazoleFluconazole may increase the effect of the benzodiazepine, alprazolam.
FosamprenavirFosamprenavir may increase the effect and toxicity of the benzodiazepine, alprazolam.
FosphenytoinFosphenytoin may increase the metabolism of alprazolam via CYP3A4.
IndinavirThe protease inhibitor, indinavir, may increase the effect of the benzodiazepine, alprazolam.
ItraconazoleItraconazole may increase the effect of the benzodiazepine, alprazolam.
JosamycinThe macrolide, josamycin, may increase the effect of the benzodiazepine, alprazolam.
KavaKava may increase the effect of the benzodiazepine, alprazolam.
KetoconazoleKetoconazole may increase the effect of the benzodiazepine, alprazolam.
MephenytoinMephenytoin may increase the metabolism of alprazolam via CYP3A4.
NelfinavirThe protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, alprazolam.
OmeprazoleOmeprazole may increase the effect of the benzodiazepine, alprazolam.
PhenytoinPhenytoin may increase the metabolism of alprazolam via CYP3A4.
RitonavirThe protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, alprazolam.
SaquinavirThe protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, alprazolam.
St. John's WortSt. John's Wort may decrease the effect of the benzodiazepine, alprazolam.
TelaprevirTelaprevir inhibits systemic metabolism of alprazolam and dose adjustment may be necessary.
TelithromycinTelithromycin may increase the effect and toxicity of the benzodiazepine, alprazolam.
TipranavirTipranavir may decrease the metabolism and clearance of Alprazolam. Consider alternate therapy or monitor for Alprazolam toxic effects if Tipranavir is initiated or dose increased.
TriprolidineThe CNS depressants, Triprolidine and Alprazolam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
VoriconazoleVoriconazole may increase the serum concentration of alprazolam by decreasing its metabolism. Monitor for alprazolam toxicity if voriconazole is initiated or dose increased.
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Avoid taking with grapefruit juice.
  • Take with food.

Targets

1. GABA-A receptor (anion channel)

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: positive allosteric modulator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details
Gamma-aminobutyric acid receptor subunit delta O14764 Details
Gamma-aminobutyric acid receptor subunit epsilon P78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details
Gamma-aminobutyric acid receptor subunit pi O00591 Details
Gamma-aminobutyric acid receptor subunit theta Q9UN88 Details

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.×. Epub 2008 Mar 31. Pubmed
  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. Pubmed

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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. Pubmed

2. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. 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. Pubmed

4. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on March 27, 2014 13:23