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=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

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
[Severe intoxication probably from olanzapine (Zyprexa). Beneficial effect of glucagon].
1999 Jun
Bilateral angle closure glaucoma and visual loss precipitated by antidepressant and antianxiety agents in a patient with depression.
2000 Sep-Oct
Interactions between herbal medicines and prescribed drugs: a systematic review.
2001
Benzodiazepines and anticonvulsants for social phobia (social anxiety disorder).
2001
Alprozolam poisoning.
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
Comparative study of tropisetron with the addition of dexamethasone or alprazolam in breast cancer patients receiving adjuvant chemotherapy with CEF (cyclophosphamide, epirubicin and 5-fluorouracil).
2001 Dec
[Carotid endarterectomy under remifentanil].
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
Opipramol for the treatment of generalized anxiety disorder: a placebo-controlled trial including an alprazolam-treated group.
2001 Feb
Sensitive gas chromatographic--mass spectrometric screening of acetylated benzodiazepines.
2001 Feb 23
No correlations between the urinary ratio of 6beta-hydroxycortisol to free cortisol and pharmacokinetics of alprazolam.
2001 Jul
Psychotropic drug use in Italy, 1984-99: the impact of a change in reimbursement status.
2001 Jul
Common effects of chronically administered antipanic drugs on brainstem GABA(A) receptor subunit gene expression.
2001 Jul
[Alpha-interferon and mental disorders].
2001 Jul-Aug
[Benzodiazepine consumption: survey of community pharmacies in Aquitaine].
2001 Jul-Aug
Burning mouth syndrome after taking clonazepam.
2001 Jul-Aug
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
Benzodiazepine modulation of opiate reward.
2001 May
Structural requirements of benzodiazepines for the inhibition of pig brain nitric oxide synthase.
2001 Nov 30
Delayed post-hypoxic leukoencephalopathy.
2001 Nov-Dec
[Two case reports of cerebral autosomal dominant arteriophaty with subcortical infarctions and leukoencephalopathy (CADASIL)].
2001 Oct
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
Alprazolam withdrawal and tolerance measured in the social conflict test in mice.
2001 Sep
The influence of stimulants, sedatives, and fatigue on tunnel vision: risk factors for driving and piloting.
2001 Summer
Recruiting phobic research subjects: effectiveness and cost.
2001 Winter
Full remission of panic attacks in a schizophrenic patient after switching from haloperidol to risperidone.
2001 Winter
Sensitive method for the detection of 22 benzodiazepines by gas chromatography-ion trap tandem mass spectrometry.
2002 Apr 19
Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7.
2002 Aug
Development of Cushing's syndrome after use of a herbal remedy.
2002 Dec 7
Accidental ingestion of alprazolam in 415 dogs.
2002 Feb
What did she want with Xanax?
2002 Feb 11
Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant.
2002 Jan
Alprazolam-induced panic disorder.
2002 Jan-Feb
[The application of a broard spectrum automatic rapid drug identification system in acute drug poisoning].
2002 Jun
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
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
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 May
Acute dystonic reactions to "street Xanax".
2002 May 30
Nightmares and panic disorder associated with carvedilol overdose.
2002 Nov
Self-association and cyclodextrin solubilization of drugs.
2002 Nov
Segmental ion spray LC-MS-MS analysis of benzodiazepines in hair of psychiatric patients.
2002 Oct
Neurobehavior effects in four strains of mice offspring exposed prenatally to alprazolam.
2002 Oct
Spectrofluorimetric assay for the photodegradation products of alprazolam.
2002 Oct 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
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
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WHO-ATC N05BA12
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NDF-RT N0000007542
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WHO-VATC QN05BA12
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NDF-RT N0000175694
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NCI_THESAURUS C1012
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Code System Code Type Description
IUPHAR
7111
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PRIMARY
HSDB
7207
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PRIMARY
SMS_ID
100000091908
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PRIMARY
NCI_THESAURUS
C227
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PRIMARY
DRUG BANK
DB00404
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PRIMARY
WIKIPEDIA
ALPRAZOLAM
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PRIMARY
FDA UNII
YU55MQ3IZY
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PRIMARY
INN
3426
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PRIMARY
PUBCHEM
2118
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PRIMARY
NSC
760140
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PRIMARY
RXCUI
596
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PRIMARY RxNorm
EVMPD
SUB05370MIG
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PRIMARY
CAS
28981-97-7
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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
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PRIMARY
LACTMED
Alprazolam
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PRIMARY
MERCK INDEX
m1578
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PRIMARY Merck Index
ECHA (EC/EINECS)
249-349-2
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PRIMARY