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Details

Stereochemistry ACHIRAL
Molecular Formula C17H13ClN4
Molecular Weight 308.765
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALPRAZOLAM

SMILES

CC1=NN=C2CN=C(C3=CC=CC=C3)C4=C(C=CC(Cl)=C4)N12

InChI

InChIKey=VREFGVBLTWBCJP-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C17H13ClN4
Molecular Weight 308.765
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/14978513

Alprazolam, 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. 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. CNS agents of the 1,4 benzodiazepine class presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system. Their exact mechanism of action is unknown. Benzodiazepines 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.

Originator

Curator's Comment: 1981

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
XANAX

Approved Use

XANAX Tablets (alprazolam) are indicated for the management of anxiety disorder (a condition corresponding most closely to the APA Diagnostic and Statistical Manual [DSMIII-R] diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. XANAX is also indicated for the treatment of panic disorder, with or without agoraphobia. Studies supporting this claim were conducted in patients whose diagnoses corresponded closely to the DSM-III-R/IV criteria for panic disorder

Launch Date

1981
Primary
XANAX

Approved Use

XANAX Tablets (alprazolam) are indicated for the management of anxiety disorder (a condition corresponding most closely to the APA Diagnostic and Statistical Manual [DSMIII-R] diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. XANAX is also indicated for the treatment of panic disorder, with or without agoraphobia. Studies supporting this claim were conducted in patients whose diagnoses corresponded closely to the DSM-III-R/IV criteria for panic disorder

Launch Date

1981
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
17.4 ng/mL
1 g single, oral
dose: 1 g
route of administration: Oral
experiment type: SINGLE
co-administered:
ALPRAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
261 ng × h/mL
1 g single, oral
dose: 1 g
route of administration: Oral
experiment type: SINGLE
co-administered:
ALPRAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11.8 h
1 g single, oral
dose: 1 g
route of administration: Oral
experiment type: SINGLE
co-administered:
ALPRAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
2.2 h
unknown
ALPRAZOLAM plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
20%
unknown
ALPRAZOLAM plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1 mg 1 times / week multiple, oral
Dose: 1 mg, 1 times / week
Route: oral
Route: multiple
Dose: 1 mg, 1 times / week
Sources:
unhealthy
n = 85
Health Status: unhealthy
Condition: Migraine
Population Size: 85
Sources:
Other AEs: Nausea, Fatigue...
Other AEs:
Nausea (below serious, 3 patients)
Fatigue (below serious, 14 patients)
Dizziness (below serious, 26 patients)
Headache (below serious, 6 patients)
Lethargy (below serious, 3 patients)
Somnolence (below serious, 45 patients)
Hiccups (below serious, 5 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Fatigue below serious, 14 patients
1 mg 1 times / week multiple, oral
Dose: 1 mg, 1 times / week
Route: oral
Route: multiple
Dose: 1 mg, 1 times / week
Sources:
unhealthy
n = 85
Health Status: unhealthy
Condition: Migraine
Population Size: 85
Sources:
Dizziness below serious, 26 patients
1 mg 1 times / week multiple, oral
Dose: 1 mg, 1 times / week
Route: oral
Route: multiple
Dose: 1 mg, 1 times / week
Sources:
unhealthy
n = 85
Health Status: unhealthy
Condition: Migraine
Population Size: 85
Sources:
Lethargy below serious, 3 patients
1 mg 1 times / week multiple, oral
Dose: 1 mg, 1 times / week
Route: oral
Route: multiple
Dose: 1 mg, 1 times / week
Sources:
unhealthy
n = 85
Health Status: unhealthy
Condition: Migraine
Population Size: 85
Sources:
Nausea below serious, 3 patients
1 mg 1 times / week multiple, oral
Dose: 1 mg, 1 times / week
Route: oral
Route: multiple
Dose: 1 mg, 1 times / week
Sources:
unhealthy
n = 85
Health Status: unhealthy
Condition: Migraine
Population Size: 85
Sources:
Somnolence below serious, 45 patients
1 mg 1 times / week multiple, oral
Dose: 1 mg, 1 times / week
Route: oral
Route: multiple
Dose: 1 mg, 1 times / week
Sources:
unhealthy
n = 85
Health Status: unhealthy
Condition: Migraine
Population Size: 85
Sources:
Hiccups below serious, 5 patients
1 mg 1 times / week multiple, oral
Dose: 1 mg, 1 times / week
Route: oral
Route: multiple
Dose: 1 mg, 1 times / week
Sources:
unhealthy
n = 85
Health Status: unhealthy
Condition: Migraine
Population Size: 85
Sources:
Headache below serious, 6 patients
1 mg 1 times / week multiple, oral
Dose: 1 mg, 1 times / week
Route: oral
Route: multiple
Dose: 1 mg, 1 times / week
Sources:
unhealthy
n = 85
Health Status: unhealthy
Condition: Migraine
Population Size: 85
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
minor
minor
minor
yes (pharmacogenomic study)
Comment: [PMID:16765147]:CYP3A5*3 genotype affects the disposition of alprazolam and thus influences the plasma levels of alprazolam
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
PubMed

PubMed

TitleDatePubMed
High-speed liquid chromatography/tandem mass spectrometry using a monolithic column for high-throughput bioanalysis.
2001
Gabapentin use in benzodiazepine dependence and detoxification.
2001 Apr
Effect of alosetron on the pharmacokinetics of alprazolam.
2001 Apr
Effects of alprazolam, caffeine, and zolpidem in humans trained to discriminate triazolam from placebo.
2001 Feb 1
Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray.
2001 Jan 5
Common effects of chronically administered antipanic drugs on brainstem GABA(A) receptor subunit gene expression.
2001 Jul
Delayed post-hypoxic leukoencephalopathy.
2001 Nov-Dec
Differential effects of alprazolam on the baseline and fear-potentiated startle reflex in humans: a dose-response study.
2001 Oct
Inverse agonist activity of selected ligands of platelet-activating factor receptor.
2001 Oct
Effects of alprazolam and fluoxetine on morphine sensitization in mice.
2002
Augmentation of analgesic effect of ibuprofen by alprazolam in experimental model of pain.
2002
What did she want with Xanax?
2002 Feb 11
GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background.
2002 Jun 28
Neuropeptide Y-Y2 receptors mediate anxiety in the amygdala.
2002 Mar
A population-based case-control teratologic study of nitrazepam, medazepam, tofisopam, alprazolum and clonazepam treatment during pregnancy.
2002 Mar 10
Acute dystonic reactions to "street Xanax".
2002 May 30
Nightmares and panic disorder associated with carvedilol overdose.
2002 Nov
Neurobehavior effects in four strains of mice offspring exposed prenatally to alprazolam.
2002 Oct
Effects of GABA(A) compounds on mCPP drug discrimination in rats.
2002 Oct 18
The effects of alprazolam and buspirone in light and moderate female social drinkers.
2002 Sep
Benzodiazepines and anterior pituitary function.
2002 Sep
Patents

Sample Use Guides

Tablets may be administered once daily, preferably in the morning. The tablets should be taken intact; they should not be chewed, crushed, or broken. The suggested total daily dose ranges between 3 to 6 mg/day. Dosage should be individualized for maximum beneficial effect
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:17:53 GMT 2023
Edited
by admin
on Fri Dec 15 15:17:53 GMT 2023
Record UNII
YU55MQ3IZY
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALPRAZOLAM
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   VANDF   WHO-DD  
INN   USAN  
Official Name English
ALPRAZOLAM [EP MONOGRAPH]
Common Name English
ALPRAZOLAM [ORANGE BOOK]
Common Name English
8-Chloro-1-methyl-6-phenyl-4H-S-triazolo[4,3-α][1,4]benzodiazepine
Common Name English
ALPRAZOLAM [USP MONOGRAPH]
Common Name English
ALPRAZOLAM [HSDB]
Common Name English
ALPRAZOLAM [MI]
Common Name English
NSC-760140
Code English
4H-(1,2,4)TRIAZOLO(4,3-.ALPHA.)(1,4)BENZODIAZEPINE, 8-CHLORO-1-METHYL-6-PHENYL-
Common Name English
ALPRAZOLAM CIV
USP-RS  
Common Name English
XANAX
Brand Name English
U-31,889
Code English
ALPRAZOLAM [JAN]
Common Name English
Alprazolam [WHO-DD]
Common Name English
U 31,889
Code English
NIRAVAM
Brand Name English
U-31889
Code English
ALPRAZOLAM [MART.]
Common Name English
alprazolam [INN]
Common Name English
ALPRAZOLAM [EP IMPURITY]
Common Name English
ALPRAZOLAM [USAN]
Common Name English
ALPRAZOLAM [VANDF]
Common Name English
Classification Tree Code System Code
LIVERTOX NBK548178
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
DEA NO. 2882
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
WHO-ATC N05BA12
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
NDF-RT N0000007542
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
WHO-VATC QN05BA12
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
NDF-RT N0000175694
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
NCI_THESAURUS C1012
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
Code System Code Type Description
IUPHAR
7111
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
HSDB
7207
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
SMS_ID
100000091908
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
NCI_THESAURUS
C227
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
DRUG BANK
DB00404
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
WIKIPEDIA
ALPRAZOLAM
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
FDA UNII
YU55MQ3IZY
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
INN
3426
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PRIMARY
PUBCHEM
2118
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
NSC
760140
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
RXCUI
596
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY RxNorm
EVMPD
SUB05370MIG
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
CAS
28981-97-7
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
CHEBI
2611
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
EPA CompTox
DTXSID4022577
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
DRUG CENTRAL
136
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PRIMARY
DAILYMED
YU55MQ3IZY
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
RS_ITEM_NUM
1015008
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
ChEMBL
CHEMBL661
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
MESH
D000525
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
LACTMED
Alprazolam
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
MERCK INDEX
m1578
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY Merck Index
ECHA (EC/EINECS)
249-349-2
Created by admin on Fri Dec 15 15:17:53 GMT 2023 , Edited by admin on Fri Dec 15 15:17:53 GMT 2023
PRIMARY
Related Record Type Details
DERIVATIVE -> PARENT
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
SOLVATE->ANHYDROUS
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
BASIS OF STRENGTH->SUBSTANCE
CHROMATOGRAPHIC PURITY (TLC)
EP
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE ACTIVE -> PARENT
α-Hydroxy alprazolam (α-OHALP) is the minor but pharmacologically active metabolite
MINOR
METABOLITE ACTIVE -> PARENT
METABOLITE LESS ACTIVE -> PARENT
4-hydroxy alprazolam (4-OHALP) is the major and pharmacologically less active metabolite [of alprazolam]
MAJOR
METABOLITE LESS ACTIVE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
RENAL CLEARANCE PHARMACOKINETIC
MAXIMUM TOLERATED DOSE TOXICITY ROUTE OF ADMINISTRATION

Biological Half-life PHARMACOKINETIC EXTENDED-RELEASE

ORALLY DISINTEGRATING TABLET

ALCOHOLIC LIVER DISEASE

ELDERLY

Volume of Distribution PHARMACOKINETIC
ORAL BIOAVAILABILITY PHARMACOKINETIC IMMEDIATE-RELEASE
PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL, IMMEDIATE-RELEASE TABLET

ORAL, EXTENDED-RELEASE TABLET