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

Details

Stereochemistry ACHIRAL
Molecular Formula C17H13ClN4.2H2O
Molecular Weight 344.795
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALPRAZOLAM DIHYDRATE

SMILES

O.O.CC1=NN=C2CN=C(C3=CC=CC=C3)C4=CC(Cl)=CC=C4N12

InChI

InChIKey=BTXVPVVNJNBVPC-UHFFFAOYSA-N
InChI=1S/C17H13ClN4.2H2O/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;2*1H2

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
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
Alprozolam poisoning.
2001 Apr
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
[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
Open study of effects of alprazolam on seasonal affective disorder.
2001 Feb
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
Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray.
2001 Jan 5
Psychotropic drug use in Italy, 1984-99: the impact of a change in reimbursement status.
2001 Jul
Psychosis after ultrarapid opiate detoxification.
2001 Jun
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
Alprazolam withdrawal and tolerance measured in the social conflict test in mice.
2001 Sep
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
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
Orally delivered alprazolam, diazepam, and triazolam as reinforcers in rhesus monkeys.
2002 Apr
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
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
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
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
Isolation and structural elucidation of degradation products of alprazolam: photostability studies of alprazolam tablets.
2002 May
Nightmares and panic disorder associated with carvedilol overdose.
2002 Nov
Self-association and cyclodextrin solubilization of drugs.
2002 Nov
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
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
Spectrofluorimetric assay for the photodegradation products of alprazolam.
2002 Oct 15
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
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
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 Dec 15 19:39:22 GMT 2023
Edited
by admin
on Fri Dec 15 19:39:22 GMT 2023
Record UNII
2I8KVA57TM
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALPRAZOLAM DIHYDRATE
Common Name English
Code System Code Type Description
CAS
135748-32-2
Created by admin on Fri Dec 15 19:39:22 GMT 2023 , Edited by admin on Fri Dec 15 19:39:22 GMT 2023
PRIMARY
FDA UNII
2I8KVA57TM
Created by admin on Fri Dec 15 19:39:22 GMT 2023 , Edited by admin on Fri Dec 15 19:39:22 GMT 2023
PRIMARY
PUBCHEM
178274
Created by admin on Fri Dec 15 19:39:22 GMT 2023 , Edited by admin on Fri Dec 15 19:39:22 GMT 2023
PRIMARY
EPA CompTox
DTXSID00159507
Created by admin on Fri Dec 15 19:39:22 GMT 2023 , Edited by admin on Fri Dec 15 19:39:22 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
ANHYDROUS->SOLVATE