U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

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=CC(Cl)=CC=C4N12

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
Health Status: unhealthy
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
Health Status: unhealthy
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
Health Status: unhealthy
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
Health Status: unhealthy
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
Health Status: unhealthy
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
Health Status: unhealthy
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
Health Status: unhealthy
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
Health Status: unhealthy
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
Alprazolam and hypotension.
1999 May
Interactions between herbal medicines and prescribed drugs: a systematic review.
2001
Comorbidity, neurobiology, and pharmacotherapy of social anxiety disorder.
2001
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
[Does the addition of an anxiolytic drug improve the anti-emetic effectiveness of the steroid and granisetron combination in the prophylaxis of cisplatin-induced vomiting?].
2001 Aug 5
Repeated measurements of aldicarb in blood and urine in a case of nonfatal poisoning.
2001 Dec
Simultaneous determination of fifteen low-dosed benzodiazepines in human urine by solid-phase extraction and gas chromatography-mass spectrometry.
2001 Dec 25
Negligible tolerance produced by chronic intravenous alprazolam administration: a low serum drug concentration effect.
2001 Feb
Electrospray ionization gas-phase electrophoresis under ambient conditions and it's potential or high-speed separations.
2001 Feb
Anxiety-like behavior in elevated plus-maze tests in repeatedly cold-stressed mice.
2001 Feb
Effects of alprazolam, caffeine, and zolpidem in humans trained to discriminate triazolam from placebo.
2001 Feb 1
In vitro/in vivo scaling of alprazolam metabolism by CYP3A4 and CYP3A5 in humans.
2001 Mar
Analytical methodology for the detection of benzodiazepine consumption in opioid-dependent subjects.
2001 Mar
[Psychiatric and psychological aspects of premenstrual syndrome].
2001 Nov-Dec
Delayed post-hypoxic leukoencephalopathy.
2001 Nov-Dec
Augmentation of analgesic effect of ibuprofen by alprazolam in experimental model of pain.
2002
Sensitive method for the detection of 22 benzodiazepines by gas chromatography-ion trap tandem mass spectrometry.
2002 Apr 19
Utilization of psychotropic drugs in Taiwan: an overview of outpatient sector in 2000.
2002 Aug
Molecular actions of (S)-desmethylzopiclone (SEP-174559), an anxiolytic metabolite of zopiclone.
2002 Aug
Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7.
2002 Aug
Effects of alprazolam on driving ability, memory functioning and psychomotor performance: a randomized, placebo-controlled study.
2002 Aug
The comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and treatment issues.
2002 Feb
Accidental ingestion of alprazolam in 415 dogs.
2002 Feb
What did she want with Xanax?
2002 Feb 11
Behavioral, psycho-physiological and salivary cortisol modifications after short-term alprazolam treatment in patients with recent myocardial infarction.
2002 Jan
Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant.
2002 Jan
Alprazolam-induced panic disorder.
2002 Jan-Feb
Effects of psychological stress and alprazolam on development of oral candidiasis in rats.
2002 Jul
Street drug toxicity resulting from opiates combined with anticholinergics.
2002 Jul-Sep
GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background.
2002 Jun 28
A comparative evaluation of the effects of oral lorazepam, alprazolam and diazepam on venous admixture.
2002 Mar
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
The orphanin receptor agonist RO 64-6198 does not induce place conditioning in rats.
2002 Mar 25
Investigation of excipient type and level on drug release from controlled release tablets containing HPMC.
2002 May
Determination of estazolam in plasma by high-performance liquid chromatography with solid-phase extraction.
2002 May
Acute dystonic reactions to "street Xanax".
2002 May 30
Nightmares and panic disorder associated with carvedilol overdose.
2002 Nov
Synthesis and biological evaluation of 7,8,9,10-tetrahydroimidazo[1,2-c]pyrido[3,4-e]pyrimdin-5(6H)-ones as functionally selective ligands of the benzodiazepine receptor site on the GABA(A) receptor.
2002 Nov 7
Clinical inquiries. What medications are effective for treating symptoms of premenstrual syndrome (PMS)?
2002 Oct
Neurobehavior effects in four strains of mice offspring exposed prenatally to alprazolam.
2002 Oct
Prenatal exposure to diazepam and alprazolam, but not to zolpidem, affects behavioural stress reactivity in handling-naïve and handling-habituated adult male rat progeny.
2002 Oct 25
Determination of hypnotic benzodiazepines (alprazolam, estazolam, and midazolam) and their metabolites in rat hair and plasma by reversed-phase liquid-chromatography with electrospray ionization mass spectrometry.
2003 Jan 15
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 Mon Mar 31 17:53:15 GMT 2025
Edited
by admin
on Mon Mar 31 17:53:15 GMT 2025
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 CIV
USP-RS  
Preferred 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-?][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
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 Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
DEA NO. 2882
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
WHO-ATC N05BA12
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
NDF-RT N0000007542
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
WHO-VATC QN05BA12
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
NDF-RT N0000175694
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
NCI_THESAURUS C1012
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
Code System Code Type Description
IUPHAR
7111
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
HSDB
7207
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
SMS_ID
100000091908
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
NCI_THESAURUS
C227
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
PRIMARY
DRUG BANK
DB00404
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
WIKIPEDIA
ALPRAZOLAM
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
PRIMARY
FDA UNII
YU55MQ3IZY
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
INN
3426
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
PRIMARY
PUBCHEM
2118
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
NSC
760140
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
RXCUI
596
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY RxNorm
EVMPD
SUB05370MIG
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
CAS
28981-97-7
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
PRIMARY
CHEBI
2611
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
EPA CompTox
DTXSID4022577
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
DRUG CENTRAL
136
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
DAILYMED
YU55MQ3IZY
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
RS_ITEM_NUM
1015008
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
ChEMBL
CHEMBL661
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
MESH
D000525
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
PRIMARY
LACTMED
Alprazolam
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY
MERCK INDEX
m1578
Created by admin on Mon Mar 31 17:53:16 GMT 2025 , Edited by admin on Mon Mar 31 17:53:16 GMT 2025
PRIMARY Merck Index
ECHA (EC/EINECS)
249-349-2
Created by admin on Mon Mar 31 17:53:15 GMT 2025 , Edited by admin on Mon Mar 31 17:53:15 GMT 2025
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