PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
alprazolam

2D structure

Overview

Generic Names: TUS-1; alprazolam
IUPAC Name: 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
Trade Names: Alplax; Alpronax; Alviz; Bestrol; Cassadan; Constan; D 65MT; Esparon; Frontal; Intensol; Niravam; Restyl; Solanax; Tafil; Tranax; Trankimazin; Tranquinal; Xanax; Xanax XR; Xanor
PharmGKB Accession Id: PA448333

Description

A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of panic disorders, with or without agoraphobia, and in generalized anxiety disorders. (From AMA Drug Evaluations Annual, 1994, p238)

Indication

For the management of anxiety disorder or the short-term relief of symptoms of anxiety and for the treatment of panic disorder, with or without agoraphobia.

ATC Therapeutic Category

  • N05BA:Benzodiazepine derivatives

Pharmacology and Interactions

Mechanism Of Action

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects 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.

Pharmacology

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. Like other triazolo benzodiazepines such as triazolam, 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.

Food Interactions

Avoid alcohol. Avoid excessive quantities of coffee or tea (Caffeine). Avoid taking with grapefruit juice. Take with food.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Hydroxylated in the liver to α-hydroxyalprazolam, which is also active. This and other metabolites are later excreted in urine as glucuronides.

Protein Binding

80% (mainly to albumin)

Absorption

Readily absorbed from the gastrointestinal tract. Bioavailability is 80-90%.

Half Life

6.3-26.9 hours

Toxicity

Oral, mouse: LD50=1020 mg/kg. Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time.

Chemical Properties

Chemical Formula:

C17H13ClN4

SMILES Code:

Cc1nnc2n1-c3ccc(cc3C(=NC2)c4ccccc4)Cl

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

308.765 / 308.0829

Curated Information

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data No genotype data No literature annotations Not annotated
ACBD3
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  • PD
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Pathways
No phenotype data No genotype data No literature annotations Not annotated
BZRAP1
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  • PD
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
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  • PK
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C19
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  • PK
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
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  • PK
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
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  • PK
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Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
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  • PK
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
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  • PK
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Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP3A43
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  • PK
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
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  • PK
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Publications
No phenotype data No genotype data Literature annotations available Not annotated
DBI
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  • PD
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
GABRA1
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  • PD
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Publications, Pathways
No phenotype data No genotype data Literature annotations available Not annotated
GABRB2
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  • PD
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Publications, Pathways
No phenotype data No genotype data Literature annotations available Not annotated
GABRG2
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Publications, Pathways
No phenotype data No genotype data No literature annotations Not annotated
SLC25A4
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  • PD
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Pathways
No phenotype data Genotype Data Available No literature annotations Not annotated
SLC32A1
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
SLC6A1
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  • PD
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
SLC6A11
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  • PD
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
SLC6A12
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  • PD
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Pathways
No phenotype data No genotype data No literature annotations Not annotated
SLC6A13
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  • PD
  • PK
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
TSPO
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  • PD
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Pathways
No phenotype data No genotype data No literature annotations Not annotated
VDAC1
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  • PD
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Pathways

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

Drug Targets

Curated Information

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available No genotype data Literature annotations available Not annotated
fluoxetine
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Publications
No phenotype data No genotype data Literature annotations available Not annotated
fluvoxamine
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Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

amprenavir Increases the effect and toxicity of benzodiazepine
aprepitant Increases the effect and toxicity of benzodiazepine
carbamazepine Reduces the effect of the benzodiazepine
cimetidine Increases the effect of the benzodiazepine
clarithromycin The macrolide increases the effect of the benzodiazepine
clozapine Increased risk of toxicity
delavirdine The antiviral agent increases the effect and toxicity of benzodiazepine
digoxin The benzodiazepine increases the effect
efavirenz The antiviral agent increases the effect and toxicity of benzodiazepine
erythromycin The macrolide increases the effect of the benzodiazepine
erythromycin The macrolide increases the effect of the benzodiazepine
ethotoin Possible increased levels of the hydantoin, decrease of benzodiazepine
fluconazole Increases the effect of the benzodiazepine
fosamprenavir Amprenavir increases the effect and toxicity of benzodiazepine
fosphenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine
indinavir The protease inhibitor increases the effect of the benzodiazepine
itraconazole The imidazole increase the effect of the benzodiazepine
josamycin The macrolide increases the effect of the benzodiazepine
kava Kava increases the effect of the benzodiazepine
ketoconazole The imidazole increases the effect of the benzodiazepine
mephenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine
nelfinavir The protease inhibitor increases the effect of the benzodiazepine
omeprazole Increases the effect of the benzodiazepine
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine
ritonavir The protease inhibitor increases the effect of the benzodiazepine
saquinavir The protease inhibitor increases the effect of the benzodiazepine
st. john's wort St. John's Wort could reduce the benzodiazepine effect
telithromycin Increases the effect/toxicity of the benzodiazepine
voriconazole The imidazole increases the effect of the benzodiazepine

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Anxiety Disorders
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  • PD
  • PK
  • FA
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Publications, Pathways
Phenotype data available No genotype data Literature annotations available Not annotated
Depression
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  • PK
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Publications
No phenotype data No genotype data Literature annotations available Not annotated
Epilepsy
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  • PD
  • PK
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
Panic Disorder
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  • PD
  • PK
  • FA
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Publications, Pathways

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Physicochemical determinants of human renal clearance

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00404
KEGG Compound ID:
C06817
KEGG Drug ID:
D00225
PubChem Compound ID:
2118
PubChem Substance ID:
176116

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
The PharmGKB is financially supported by the NIH/ NIGMS and is managed at Stanford University (U01GM61374).
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