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

Details

Stereochemistry ACHIRAL
Molecular Formula C17H13ClN4
Molecular Weight 308.7655
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALPRAZOLAM

SMILES

Cc1nnc2CN=C(c3ccccc3)c4cc(ccc4-n12)Cl

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 308.7655
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

3.72038402E11
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

3.72038402E11
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
Alprozolam poisoning.
2001 Apr
Pharmacokinetically induced benzodiazepine withdrawal.
2001 Autumn
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
[Alpha-interferon and mental disorders].
2001 Jul-Aug
In vitro/in vivo scaling of alprazolam metabolism by CYP3A4 and CYP3A5 in humans.
2001 Mar
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
[Two case reports of cerebral autosomal dominant arteriophaty with subcortical infarctions and leukoencephalopathy (CADASIL)].
2001 Oct
Alprazolam withdrawal and tolerance measured in the social conflict test in mice.
2001 Sep
Effects of alprazolam and fluoxetine on morphine sensitization in mice.
2002
Orally delivered alprazolam, diazepam, and triazolam as reinforcers in rhesus monkeys.
2002 Apr
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
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
Preoperative alprazolam reduces anxiety in ambulatory surgery patients: a comparison with oral midazolam.
2002 Dec
Development of Cushing's syndrome after use of a herbal remedy.
2002 Dec 7
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
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
[The application of a broard spectrum automatic rapid drug identification system in acute drug poisoning].
2002 Jun
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
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
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
Isolation and structural elucidation of degradation products of alprazolam: photostability studies of alprazolam tablets.
2002 May
Acute dystonic reactions to "street Xanax".
2002 May 30
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 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
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
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
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
Target-controlled infusion of propofol induction with or without plasma concentration constraint in high-risk adult patients undergoing cardiac surgery.
2002 Sep
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 Sep 15
Assay sensitivity, failed clinical trials, and the conduct of science.
2002 Sep-Oct
Discriminative stimulus effects of zolpidem in squirrel monkeys: role of GABA(A)/alpha1 receptors.
2003 Jan
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 Fri Jun 25 21:01:36 UTC 2021
Edited
by admin
on Fri Jun 25 21:01:36 UTC 2021
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]
Common 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-.ALPHA.)(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 [WHO-DD]
Common Name English
ALPRAZOLAM [JAN]
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 [USAN]
Common Name English
ALPRAZOLAM [VANDF]
Common Name English
Classification Tree Code System Code
LIVERTOX 31
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
DEA NO. 2882
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
WHO-ATC N05BA12
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
NDF-RT N0000007542
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
WHO-VATC QN05BA12
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
NDF-RT N0000175694
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
NCI_THESAURUS C1012
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
Code System Code Type Description
IUPHAR
7111
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
HSDB
7207
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
NCI_THESAURUS
C227
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
DRUG BANK
DB00404
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
WIKIPEDIA
ALPRAZOLAM
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
FDA UNII
YU55MQ3IZY
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
INN
3426
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
PUBCHEM
2118
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
RXCUI
596
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY RxNorm
EVMPD
SUB05370MIG
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
CAS
28981-97-7
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
USP_CATALOG
1015008
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY USP-RS
EPA CompTox
28981-97-7
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
DRUG CENTRAL
136
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
ChEMBL
CHEMBL661
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
MESH
D000525
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
LACTMED
Alprazolam
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
MERCK INDEX
M1578
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY Merck Index
ECHA (EC/EINECS)
249-349-2
Created by admin on Fri Jun 25 21:01:36 UTC 2021 , Edited by admin on Fri Jun 25 21:01:36 UTC 2021
PRIMARY
Related Record Type Details
DERIVATIVE -> PARENT
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
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
METABOLITE INACTIVE -> 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