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

Details

Stereochemistry ACHIRAL
Molecular Formula C17H12Cl2N4
Molecular Weight 343.2105
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIAZOLAM

SMILES

Cc1nnc2CN=C(c3ccccc3Cl)c4cc(ccc4-n12)Cl

InChI

InChIKey=JOFWLTCLBGQGBO-UHFFFAOYSA-N
InChI=1S/C17H12Cl2N4/c1-10-21-22-16-9-20-17(12-4-2-3-5-14(12)19)13-8-11(18)6-7-15(13)23(10)16/h2-8H,9H2,1H3

HIDE SMILES / InChI

Molecular Formula C17H12Cl2N4
Molecular Weight 343.2105
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/017892s038lbl.pdf

Triazolam is a short-acting benzodiazepine used as a hypnotic agent in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. Triazolam has a shorter half-life than chlordiazepoxide, flurazepam, and prazepam and does not generate active metabolites. Benzodiazepines bind nonspecifically to bezodiazepine 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 GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell. Triazolam is used for the short-term treatment of insomnia. Triazolam`s original brand name is Halcion. Triazolam is withdrawn in the United Kingdom due to risk of psychiatric adverse drug reactions. This drug continues to be available in the U.S. Internationally, triazolam is a Schedule IV drug under the Convention on Psychotropic Substances.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Halcion

Approved Use

Halcion is indicated for the short-term treatment of insomnia (generally 7–10 days). Use for more than 2–3 weeks requires complete reevaluation of the patient

Launch Date

406080000000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.75 ng/mL
0.25 mg single, oral
dose: 0.25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIAZOLAM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.39 ng/mL
0.25 mg single, oral
dose: 0.25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
13.05 ng × h/mL
0.25 mg single, oral
dose: 0.25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIAZOLAM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
13.78 ng × h/mL
0.25 mg single, oral
dose: 0.25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.07 h
0.25 mg single, oral
dose: 0.25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIAZOLAM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.27 h
0.25 mg single, oral
dose: 0.25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
3 mg single, oral
Highest studied dose
Dose: 3 mg
Route: oral
Route: single
Dose: 3 mg
Sources:
unhealthy, 21 - 60 years
Health Status: unhealthy
Age Group: 21 - 60 years
Sex: M
Sources:
Disc. AE: Ataxia, Drowsiness...
AEs leading to
discontinuation/dose reduction:
Ataxia (1 patient)
Drowsiness (1 patient)
Sources:
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Coordination abnormal, Drowsiness...
AEs leading to
discontinuation/dose reduction:
Coordination abnormal
Drowsiness
Groggy
Somnolence
Depression
Restlessness
Dizziness
Lightheadedness
Headache
Nausea
Visual disturbance
Nervousness
Abdominal distress
Bladder disorders NEC
Aching in limb
Backache
Blepharitis
Sources:
AEs

AEs

AESignificanceDosePopulation
Ataxia 1 patient
Disc. AE
3 mg single, oral
Highest studied dose
Dose: 3 mg
Route: oral
Route: single
Dose: 3 mg
Sources:
unhealthy, 21 - 60 years
Health Status: unhealthy
Age Group: 21 - 60 years
Sex: M
Sources:
Drowsiness 1 patient
Disc. AE
3 mg single, oral
Highest studied dose
Dose: 3 mg
Route: oral
Route: single
Dose: 3 mg
Sources:
unhealthy, 21 - 60 years
Health Status: unhealthy
Age Group: 21 - 60 years
Sex: M
Sources:
Abdominal distress Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Aching in limb Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Backache Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Bladder disorders NEC Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Blepharitis Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Coordination abnormal Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Depression Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Dizziness Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Drowsiness Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Groggy Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Headache Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Lightheadedness Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Nausea Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Nervousness Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Restlessness Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Somnolence Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Visual disturbance Disc. AE
0.25 mg 1 times / day steady, oral
Recommended
Dose: 0.25 mg, 1 times / day
Route: oral
Route: steady
Dose: 0.25 mg, 1 times / day
Sources:
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
yes
yes
yes (co-administration study)
Comment: contraindicated with strong CYP3A inhibitors such as ketoconazole, itraconazole, nefazodone, ritonavir, indinavir, nelfinavir, saquinavir, and lopinavir; from 2019 label: grapefruit juice increased maximum plasma concentration of triazolam by 25% and increased AUC by 48%
Page: 7
PubMed

PubMed

TitleDatePubMed
Triazolam substrate inhibition: evidence of competition for heme-bound reactive oxygen within the CYP3A4 active site.
2001
CYP3A inductive potential of the rifamycins, rifabutin and rifampin, in the rabbit.
2001 May
Triazolam impairs inhibitory control of behavior in humans.
2001 Nov
Toxicological interactions between alcohol and benzodiazepines.
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
Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7.
2002 Aug
Effect of zaleplon on learning and memory in rats.
2002 Aug
Discriminative-stimulus effects of modafinil in cocaine-trained humans.
2002 Aug 1
Alcohol and triazolam: differential effects on memory, psychomotor performance and subjective ratings of effects.
2002 Dec
A role for cryptochromes in sleep regulation.
2002 Dec 20
[Identification of estazolam, alprazolam and triazolam in human urine by LC/MSn].
2002 Feb
[Pharmacological profile and clinical effect of zolpidem (Myslee tablets), a hypnotic agent].
2002 Feb
Effects of fenfluramine, m-CPP and triazolam on repeated-acquisition in squirrel monkeys before and after neurotoxic MDMA administration.
2002 Feb
Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers.
2002 Jan
Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic.
2002 Jan 2
Distribution of triazolam and alpha-hydroxytriazolam in a fatal intoxication case.
2002 Jan-Feb
The study of polysomnography and sleepiness the morning after administration of triazolam and brotizolam.
2002 Jun
Acute performance-impairing and subject-rated effects of triazolam and temazepam, alone and in combination with ethanol, in humans.
2002 Mar
Daily treatment with diazepam differentially modifies sensitivity to the effects of gamma-aminobutyric acid(A) modulators on schedule-controlled responding in rhesus monkeys.
2002 Mar
Fulminant hepatic failure associated with triazolam.
2002 May
Role of GABAA/benzodiazepine receptors containing alpha 1 and alpha 5 subunits in the discriminative stimulus effects of triazolam in squirrel monkeys.
2002 May
Nighttime versus daytime hypnotic self-administration.
2002 May
Safety of zaleplon in the treatment of insomnia.
2002 May
Feeding melatonin enhances the phase shifting response to triazolam in both young and old golden hamsters.
2002 May
Effects of endogenous steroids on CYP3A4-mediated drug metabolism by human liver microsomes.
2002 May
Disposition of triazolam in the rat by brain microdialysis and semi-micro column high-performance liquid chromatography with UV absorbance detection.
2002 May
Selective antagonism of the ataxic effects of zolpidem and triazolam by the GABAA/alpha1-preferring antagonist beta-CCt in squirrel monkeys.
2002 Nov
Transnational industrial power, the medical profession and the regulatory state: adverse drug reactions and the crisis over the safety of Halcion in the Netherlands and the UK.
2002 Nov
Interactions between recreational drugs and antiretroviral agents.
2002 Oct
Development and use of a computer program to detect potentially inappropriate prescribing in older adults residing in Canadian long-term care facilities.
2002 Oct 14
Melatonin microinjection into the medial preoptic area increases sleep in the rat.
2002 Sep 13
Pharmacokinetic interactions with rifampicin : clinical relevance.
2003
[Cytochrome P450 3A4 and Benzodiazepines].
2003
Study of nocturnal sleep and the carryover effects of triazolam and brotizolam using neurophysiological and subjective methods.
2003
Lopinavir/ritonavir: a review of its use in the management of HIV infection.
2003
Clinical pharmacokinetic profile of modafinil.
2003
Discriminative-stimulus effects of triazolam in light and moderate drinkers.
2003 Apr
[Diagnostics and treatment of sleep disorders in elderly people].
2003 Apr-Jun
Long-, intermediate- and short-acting benzodiazepine effects on human sleep EEG spectra.
2003 Feb
Semi-micro column HPLC of triazolam in rat plasma and brain microdialysate and its application to drug interaction study with itraconazole.
2003 Jan 15
Effects of short-acting hypnotics on sleep latency in rats placed on grid suspended over water.
2003 Jan 24
In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5.
2003 Jul
Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital.
2003 Jun
Selective effects of triazolam on memory for emotional, relative to neutral, stimuli: differential effects on gist versus detail.
2003 Jun
Comparison of hangover effects among triazolam, flunitrazepam and quazepam in healthy subjects: a preliminary report.
2003 Jun
Role of platelet activating factor in triazolobenzodiazepines-induced retrograde amnesia.
2003 Jun 16
Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir.
2003 Mar
Triazolam-amphetamine interaction: dissociation of effects on memory versus arousal.
2003 Mar
Differential effects in humans after repeated administrations of zolpidem and triazolam.
2003 May
Patents

Sample Use Guides

In Vivo Use Guide
The recommended dose for most adults is 0.25 mg before retiring. A dose of 0.125 mg may be found to be sufficient for some patients (e.g., low body weight). A dose of 0.5 mg should be used only for exceptional patients who do not respond adequately to a trial of a lower dose since the risk of several adverse reactions increases with the size of the dose administered. A dose of 0.5 mg should not be exceeded.
Route of Administration: Oral
In Vitro Use Guide
Triazolam inhibited [3H]flunitrazepam binding with an IC50 value of 0.85 nM and a Ki value of 0.50 nM in mice.
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:55:03 UTC 2021
Edited
by admin
on Fri Jun 25 20:55:03 UTC 2021
Record UNII
1HM943223R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRIAZOLAM
HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   VANDF   WHO-DD  
USAN   INN  
Official Name English
TRIAZOLAM [HSDB]
Common Name English
N05CD05
Code English
TRIAZOLAM [JAN]
Common Name English
U-33,030
Code English
TRIAZOLAM [MART.]
Common Name English
TRIAZOLAM [VANDF]
Common Name English
4H-(1,2,4)TRIAZOLO(4,3-A)(1,4)BENZODIAZEPINE, 8-CHLORO-6-(2-CHLOROPHENYL)-1-METHYL-
Systematic Name English
TRIAZOLAM [MI]
Common Name English
U-33030
Code English
TRIAZOLAM [INN]
Common Name English
TRIAZOLAM [USAN]
Common Name English
TRIAZOLAM [WHO-DD]
Common Name English
TRIAZOLAM [ORANGE BOOK]
Common Name English
TRIAZOLAM [USP MONOGRAPH]
Common Name English
8-CHLORO-6-(O-CHLOROPHENYL)-1-METHYL-4H-S-TRIAZOLO(4,3-A)(1,4)BENZODIAZEPINE
Common Name English
TRIAZOLAM CIV [USP-RS]
Common Name English
HALCION
Brand Name English
TRIAZOLAM CIV
USP-RS  
Common Name English
Classification Tree Code System Code
WHO-VATC QN05CD05
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
NDF-RT N0000007542
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
NCI_THESAURUS C1012
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
NDF-RT N0000175694
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
LIVERTOX 996
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
DEA NO. 2887
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
WHO-ATC N05CD05
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
Code System Code Type Description
FDA UNII
1HM943223R
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
HSDB
6759
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
DRUG CENTRAL
2729
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
DRUG BANK
DB00897
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
EPA CompTox
28911-01-5
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
MERCK INDEX
M11035
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1680506
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY USP-RS
ECHA (EC/EINECS)
249-307-3
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
WIKIPEDIA
TRIAZOLAM
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
ChEMBL
CHEMBL646
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
PUBCHEM
5556
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
CAS
28911-01-5
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
INN
3409
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
MESH
D014229
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
RXCUI
10767
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY RxNorm
IUPHAR
7313
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
LACTMED
Triazolam
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
NCI_THESAURUS
C29520
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
EVMPD
SUB11258MIG
Created by admin on Fri Jun 25 20:55:03 UTC 2021 , Edited by admin on Fri Jun 25 20:55:03 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC