U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
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.
2003-01-15
Discriminative stimulus effects of zolpidem in squirrel monkeys: role of GABA(A)/alpha1 receptors.
2003-01
Development of Cushing's syndrome after use of a herbal remedy.
2002-12-07
Preoperative alprazolam reduces anxiety in ambulatory surgery patients: a comparison with oral midazolam.
2002-12
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.
2002-11-07
Nightmares and panic disorder associated with carvedilol overdose.
2002-11
5-ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydrobenzo[4,5]imidazo[1,2a]pyridine-4-N-(2-fluorophenyl)carboxamide (RWJ-51204), a new nonbenzodiazepine anxiolytic.
2002-11
Self-association and cyclodextrin solubilization of drugs.
2002-11
Prenatal exposure to diazepam and alprazolam, but not to zolpidem, affects behavioural stress reactivity in handling-naïve and handling-habituated adult male rat progeny.
2002-10-25
Effects of GABA(A) compounds on mCPP drug discrimination in rats.
2002-10-18
Spectrofluorimetric assay for the photodegradation products of alprazolam.
2002-10-15
Segmental ion spray LC-MS-MS analysis of benzodiazepines in hair of psychiatric patients.
2002-10
Clinical inquiries. What medications are effective for treating symptoms of premenstrual syndrome (PMS)?
2002-10
Neurobehavior effects in four strains of mice offspring exposed prenatally to alprazolam.
2002-10
The stimulatory effect of canrenoate, a mineralocorticoid antagonist, on the activity of the hypothalamus-pituitary-adrenal axis is abolished by alprazolam, a benzodiazepine, in humans.
2002-10
Suppression of monocyte chemoattractant protein 1, but not IL-8, by alprazolam: effect of alprazolam on c-Rel/p65 and c-Rel/p50 binding to the monocyte chemoattractant protein 1 promoter region.
2002-09-15
Assay sensitivity, failed clinical trials, and the conduct of science.
2002-09-11
The effects of alprazolam and buspirone in light and moderate female social drinkers.
2002-09
Don't ask, don't tell, but benzodiazepines are still the leading treatments for anxiety disorder.
2002-09
Benzodiazepines and anterior pituitary function.
2002-09
Selective serotonin reuptake inhibitors decrease impulsive behavior as measured by an adjusting delay procedure in the pigeon.
2002-09
Target-controlled infusion of propofol induction with or without plasma concentration constraint in high-risk adult patients undergoing cardiac surgery.
2002-09
Utilization of psychotropic drugs in Taiwan: an overview of outpatient sector in 2000.
2002-08
Molecular actions of (S)-desmethylzopiclone (SEP-174559), an anxiolytic metabolite of zopiclone.
2002-08
Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7.
2002-08
Effects of alprazolam on driving ability, memory functioning and psychomotor performance: a randomized, placebo-controlled study.
2002-08
Street drug toxicity resulting from opiates combined with anticholinergics.
2002-07-12
Tonic immobility in guinea pigs: a behavioural response for detecting an anxiolytic-like effect?
2002-07
Effects of psychological stress and alprazolam on development of oral candidiasis in rats.
2002-07
GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background.
2002-06-28
[The application of a broard spectrum automatic rapid drug identification system in acute drug poisoning].
2002-06
Acute dystonic reactions to "street Xanax".
2002-05-30
Investigation of excipient type and level on drug release from controlled release tablets containing HPMC.
2002-05
Determination of estazolam in plasma by high-performance liquid chromatography with solid-phase extraction.
2002-05
Alprazolam, a benzodiazepine, does not modify the ACTH and cortisol response to hCRH and AVP, but blunts the cortisol response to ACTH in humans.
2002-05
Isolation and structural elucidation of degradation products of alprazolam: photostability studies of alprazolam tablets.
2002-05
Sensitive method for the detection of 22 benzodiazepines by gas chromatography-ion trap tandem mass spectrometry.
2002-04-19
Orally delivered alprazolam, diazepam, and triazolam as reinforcers in rhesus monkeys.
2002-04
Influence of the 5-HT2C receptor antagonist, SB-242084, in tests of anxiety.
2002-04
The orphanin receptor agonist RO 64-6198 does not induce place conditioning in rats.
2002-03-25
A comparative evaluation of the effects of oral lorazepam, alprazolam and diazepam on venous admixture.
2002-03
[Psychiatric and psychological aspects of premenstrual syndrome].
2002-02-28
What did she want with Xanax?
2002-02-11
The comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and treatment issues.
2002-02
Behavioral, psycho-physiological and salivary cortisol modifications after short-term alprazolam treatment in patients with recent myocardial infarction.
2002-01
Effects of alprazolam and fluoxetine on morphine sensitization in mice.
2002
Differential metabolism of alprazolam by liver and brain cytochrome (P4503A) to pharmacologically active metabolite.
2002
Augmentation of analgesic effect of ibuprofen by alprazolam in experimental model of pain.
2002
Repeated measurements of aldicarb in blood and urine in a case of nonfatal poisoning.
2001-12
Pharmacokinetically induced benzodiazepine withdrawal.
2001
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
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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
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PRIMARY
NCI_THESAURUS
C227
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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
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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
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PRIMARY
PUBCHEM
2118
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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
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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
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PRIMARY
EPA CompTox
DTXSID4022577
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PRIMARY
DRUG CENTRAL
136
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PRIMARY
DAILYMED
YU55MQ3IZY
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PRIMARY
RS_ITEM_NUM
1015008
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PRIMARY
ChEMBL
CHEMBL661
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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