General
Preferred name
ALPRAZOLAM
Synonyms
Xanax Xr ()
Xanax ()
U-31889 ()
Alprazolam civ ()
U-31,889 ()
U 31,889 ()
NSC-760140 ()
Niravam ()
Alprazolam-d8 ()
Alprazolam-d5 (CRM) ()
Alprazolam-d3 ()
Alprazolam-d8 (exempt preparation) ()
Alprazolam-d3 (exempt preparation) ()
P&D ID
PD003153
CAS
28981-97-7
1246182-61-5
2749394-85-0
125229-61-0
112393-64-3
Tags
natural product
drug
available
Approved by
FDA
First approval
1981
Drug Status
illicit
investigational
approved
Drug indication
Epilepsy
Anxiety disorder
Sedative-Hypnotic
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Alprazolam is indicated to treat anxiety and panic disorders.[Label] The mechanism by which its cell receptor interactions translate to a clinical effect is not known.[Label,A177973,A18125]; ; Alprazolam exerts its effects through interaction with BNZ-1, BNZ-2, and GABA-A receptors.[A177973,A18125] Alprazolam binding to BNZ-1 is thought to influence sedation and anti-anxiety, BNZ-2 may influence memory, coordination, muscle relaxation, and anticonvulsive activity, and GABA-A may calm patients by increasing the affinity of GABA-A receptors for GABA[A177973,A18125].; ; The metabolism of alprazolam is mediated largely through the action of CYP3As and so alprazolam is contraindicated with CYP3A inhibitors such as ketoconazole and itraconazole.[Label]; ; Alprazolam, like other benzodiazepines, can cause dependancy and so when stopping treatment doses should be tapered down gradually[A18125]. Alprazolam's adverse effects are generally related to the sedating effects of the drug.[A18125] This effect has lead to abuse of alprazolam with alcohol to potentiate its sedating effect, which may lead to coma and death.[A18125]
INDICATION
Alprazolam is indicated for the management of anxiety disorder, anxiety associated with depression, panic disorder, and panic disorder with agoraphobia.[Label] Alprazolam may also be prescribed off label for insomnia, premenstrual syndrome, and depression.[A177973]
ROE
Alprazolam is mainly eliminated in the urine.[Label] A large portion of the dose is eliminated as unmetabolized alprazolam.[A177925] <10% of the dose is eliminated as alpha-hydroxy-alprazolam and 4-hydroxy-alprazolam.[A177925]
TOXICITY
Alprazolam overdose can present as sleepiness, confusion, poor coordination, slow reflexes, coma, and death.[Label] Taking alprazolam with alcohol lowers the threshold for overdose.[Label] Patients should have their respiration, pulse, and blood pressure monitored.[Label] Patients can be treated by gastric lavage and intravenous fluids.[Label]. If hypotension occurs, patients may be treated with vasopressors.[Label] In known, or suspected overdoses, patients can be given the benzodiazepine receptor antagonist [flumazenil] in addition to other methods of management.[Label]; ; Oral LD50 in rats is 331-2171mg/kg.[Label]; ; Alprazolam is a pregnancy category D teratogen meaning there is evidence of risk to the fetus of a mother taking alprazolam but in some cases the benefit may outweigh the risk.[Label,L6172] Children born to these mothers are also at risk of withdrawal symptoms, flaccidity, and respiratory issues.[Label]; ; Benzodiazepines are expressed in human breast milk and so nursing is generally not recommended in mothers taking alprazolam.[Label]; ; Alprazolam is not associated with carcinogenicity, mutagenicity, or impairment of fertility.[Label]
METABOLISM
Alprazolam is metabolized to less effective metabolites by various CYPs including CYP3A4, CYP3A5, CYP3A7, and CYP2C9.[Label,A415,A14710,A14775,L162] The majority of alprazolam metabolism is mediated by hydroxylation via CYP3As.[Label,A415,A14710,A14775,A177925,L162] 4-hydroxyalprazolam has 20% the binding affinity of the parent drug, alpha-hydroxyalprazolam has 66% the affinity, and the benzophenone metabolite has <1% the affinity.[Label,A177925]
HALF-LIFE
11.2 hours in healthy patients.[Label] The half life is 16.3h in the elderly, 5.8-65.3h in patients with alcoholic liver disease, 9.9-40.4h in obese patients.[Label] The half life is 25% higher in Asian patients compared to Caucasians.[Label] Other studies have shown the half life to be 9-16h.[A177925]
DESCRIPTION
Alprazolam is a benzodiazepine drug.
(GtoPdb)
MOA
Alprazolam is a triazolobenzodiazepine used to treat certain anxiety and panic disorders.[Label] Alprazolam acts on benzodiazepine receptors BNZ-1 and BNZ-2.[Label,A177973,A177925] The active metabolites 4-hydroxyalprazolam acts on these receptors with 0.20 times the potency of alprazolam and alpha-hydroxyalprazolam acts on these receptors with 0.66 times the potency.[Label]; ; The effect of alprazolam on BNZ-1 mediates the sedation and anti-anxiety effects of the drug while the action on BNZ-2 mediates effects on memory, coordination, muscle relaxation, and anticonvulsive activity.[A177973,A18125]; ; Alprazolam also couple with GABA-A receptors to enhance GABA binding to its receptor.[A177973] This interaction mediates inhibition of the nervous system and results in a calming effect.[A177973]; ; The molecular mechanisms as well as the clinical effects of alprazolam have both been well demonstrated, however the means by which the molecular mechanism translates to a clinical effect is still not understood.[Label,A177973,A18125]
ABSORPTION
Oral bioavailability of a standard release tablet of alprazolam is 84-91% with a time to maximum concentration of 1.8 hours.[A177925] A 1mg oral dose of alprazolam leads to a maximum plasma concentration of 12-22mcg/L.[A177925] Alprazolam is rapidly absorbed in the gastrointestinal tract.[A177925]; ; Data for the area under the curve and the effect of taking alprazolam with food are not readily available.[Label]
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
1
Compound Sets
25
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Guide to Pharmacology
IPPI - DB
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
ReFrame library
ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
48
Molecular Weight
308.08
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
0
Rotatable Bonds
1
Ring Count
4
Aromatic Ring Count
3
cLogP
3.58
TPSA
43.07
Fraction CSP3
0.12
Chiral centers
0.0
Largest ring
7.0
QED
0.69
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Member status
virtual
MOA
GABA(A) BZ Site Receptor Agonists
Therapeutic Class
Hypnotics and Sedatives
Source data
