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
Interactions between herbal medicines and prescribed drugs: a systematic review.
2001
Comorbidity, neurobiology, and pharmacotherapy of social anxiety disorder.
2001
Benzodiazepines and anticonvulsants for social phobia (social anxiety disorder).
2001
Gabapentin use in benzodiazepine dependence and detoxification.
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
Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam.
2001 Feb
Opipramol for the treatment of generalized anxiety disorder: a placebo-controlled trial including an alprazolam-treated group.
2001 Feb
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
No correlations between the urinary ratio of 6beta-hydroxycortisol to free cortisol and pharmacokinetics of alprazolam.
2001 Jul
[Alpha-interferon and mental disorders].
2001 Jul-Aug
[Benzodiazepine consumption: survey of community pharmacies in Aquitaine].
2001 Jul-Aug
Psychosis after ultrarapid opiate detoxification.
2001 Jun
In vitro/in vivo scaling of alprazolam metabolism by CYP3A4 and CYP3A5 in humans.
2001 Mar
Spontaneous activity as a contingency-controlled behavior within an operant context: alprazolam concentration-effect relations after subcutaneous administration in rats.
2001 May
Structural requirements of benzodiazepines for the inhibition of pig brain nitric oxide synthase.
2001 Nov 30
[Psychiatric and psychological aspects of premenstrual syndrome].
2001 Nov-Dec
Delayed post-hypoxic leukoencephalopathy.
2001 Nov-Dec
Inverse agonist activity of selected ligands of platelet-activating factor receptor.
2001 Oct
Full remission of panic attacks in a schizophrenic patient after switching from haloperidol to risperidone.
2001 Winter
Effects of alprazolam and fluoxetine on morphine sensitization in mice.
2002
Influence of the 5-HT2C receptor antagonist, SB-242084, in tests of anxiety.
2002 Apr
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
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
Tonic immobility in guinea pigs: a behavioural response for detecting an anxiolytic-like effect?
2002 Jul
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
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
Determination of estazolam in plasma by high-performance liquid chromatography with solid-phase extraction.
2002 May
Segmental ion spray LC-MS-MS analysis of benzodiazepines in hair of psychiatric patients.
2002 Oct
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 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
Don't ask, don't tell, but benzodiazepines are still the leading treatments for anxiety disorder.
2002 Sep
Benzodiazepines and anterior pituitary function.
2002 Sep
Selective serotonin reuptake inhibitors decrease impulsive behavior as measured by an adjusting delay procedure in the pigeon.
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
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