TRIAZOLAM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H12Cl2N4
Molecular Weight	343.21
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=NN=C2CN=C(C3=CC=CC=C3Cl)C4=CC(Cl)=CC=C4N12

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

Description
Sources: http://www.drugbank.ca/drugs/DB00897
Curator's Comment: Description was created based on several sources, including 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 Triazolam is withdrawn in the United Kingdom due to risk of psychiatric adverse drug reactions.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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
GABA-A receptor; anion channel 203 Target ID: CHEMBL2093872 Sources: http://www.genome.jp/dbget-bin/www_bget?D00387 \| http://www.drugbank.ca/drugs/DB00897 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/017892s038lbl.pdf	Agonist 2752	0.8 nM [Ki]
GABA-A receptor; alpha-2/beta-3/gamma-2 12 Target ID: CHEMBL2094130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10633039	Agonist 2752	0.59 nM [Ki]
GABA-A receptor; alpha-1/beta-3/gamma-2 16 Target ID: CHEMBL2094121 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10633039	Agonist 2752	0.8 nM [Ki]
GABA-A receptor; alpha-3/beta-3/gamma-2 11 Target ID: CHEMBL2094120 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10633039	Agonist 2752	1.43 nM [Ki]
GABA-A receptor; alpha-5/beta-3/gamma-2 14 Target ID: CHEMBL2094122 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10633039	Agonist 2752	1.54 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Insomnia 111 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/017892s038lbl.pdf	Primary		Approved 8583	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 1982

C_max

Value	Dose	Analyte	Population
4.39 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8275618/	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
3.75 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8275618/	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
1.69 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	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: UNKNOWN
0.91 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered:	.ALPHA.-HYDROXYTRIAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.05 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered:	.ALPHA.-HYDROXYTRIAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.69 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	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: UNKNOWN

AUC

Value	Dose	Analyte	Population
13.78 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8275618/	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
13.05 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8275618/	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
9.93 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	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: UNKNOWN
5.88 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered:	.ALPHA.-HYDROXYTRIAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.99 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered:	.ALPHA.-HYDROXYTRIAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	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: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.27 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8275618/	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
4.07 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8275618/	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
3.18 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	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: UNKNOWN
5.54 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered:	.ALPHA.-HYDROXYTRIAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.49 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered:	.ALPHA.-HYDROXYTRIAZOLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.48 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11503006/	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: UNKNOWN

Doses

Dose	Population	Adverse events
3 mg single, oral Highest studied dose Dose: 3 mg Route: oral Route: single Dose: 3 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19327	unhealthy, 21 - 60 years Health Status: unhealthy Age Group: 21 - 60 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/19327	Disc. AE: Ataxia, Drowsiness... AEs leading to discontinuation/dose reduction: Ataxia (1 patient) Drowsiness (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19327
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/017892s050lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/017892s050lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/017892s050lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 725	CYP3A 220 P-gp 2052

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21561794/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15258104/	no
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16158798/	yes
CYP3A 220	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/017892s055lbl.pdf Page: 7.0	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% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/017892s055lbl.pdf Page: 7.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9674	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9674
eMolecules	595231	https://www.emolecules.com/cgi-bin/more?vid=595231
ZINC	ZINC000000002212	http://zinc15.docking.org/substances/ZINC000000002212

PubMed

Title	Date	PubMed
Central serotonergic mechanisms on head twitch response induced by benzodiazepine receptor agonists.	2001	11287817
Effect of ranitidine on the pharmacokinetics of triazolam and alpha-hydroxytriazolam in both young (19-60 years) and older (61-78 years) people.	2001 Aug	11503006
Determination of triazolam involving its hydroxy metabolites in hair shaft and hair root by reversed-phase liquid chromatography with electrospray ionization mass spectrometry and application to human hair analysis.	2001 Aug 15	11488619
Behavioral pharmacological similarities between methylphenidate and cocaine in cocaine abusers.	2001 Feb	11519636
Acute dose-effects of scopolamine on false recognition.	2001 Feb	11243489
Sensitive gas chromatographic--mass spectrometric screening of acetylated benzodiazepines.	2001 Feb 23	11263563
Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors.	2001 Jan	11225565
Triazolam substrate inhibition: evidence of competition for heme-bound reactive oxygen within the CYP3A4 active site.	2001 Jan	11124232
Sleep inducing effects of propofol microinjection into the medial preoptic area are blocked by flumazenil.	2001 Jul 27	11454326
CYP3A inductive potential of the rifamycins, rifabutin and rifampin, in the rabbit.	2001 May	11745918
Retrograde facilitation of memory by triazolam: effects on automatic processes.	2001 Nov	11713622
Isobolographic analysis of chlordiazepoxide and triazolam combinations in squirrel monkeys discriminating triazolam.	2001 Nov	11702092
Effect of methylprednisolone on CYP3A4-mediated drug metabolism in vivo.	2001 Sep	11699609
Tolerability of hypnosedatives in older patients.	2002	12182689
Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications.	2002	12126458
Toxicological interactions between alcohol and benzodiazepines.	2002	11990206
Sensitive method for the detection of 22 benzodiazepines by gas chromatography-ion trap tandem mass spectrometry.	2002 Apr 19	12058908
Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7.	2002 Aug	12124305
Effect of zaleplon on learning and memory in rats.	2002 Aug	12122506
Discriminative-stimulus effects of modafinil in cocaine-trained humans.	2002 Aug 1	12127202
Alcohol and triazolam: differential effects on memory, psychomotor performance and subjective ratings of effects.	2002 Dec	12478216
[Identification of estazolam, alprazolam and triazolam in human urine by LC/MSn].	2002 Feb	12579961
[Pharmacological profile and clinical effect of zolpidem (Myslee tablets), a hypnotic agent].	2002 Feb	11862759
Effects of fenfluramine, m-CPP and triazolam on repeated-acquisition in squirrel monkeys before and after neurotoxic MDMA administration.	2002 Feb	11823891
Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers.	2002 Jan	11823757
Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic.	2002 Jan 2	11755161
Distribution of triazolam and alpha-hydroxytriazolam in a fatal intoxication case.	2002 Jan-Feb	11888017
The study of polysomnography and sleepiness the morning after administration of triazolam and brotizolam.	2002 Jun	12047603
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	11861811
Fulminant hepatic failure associated with triazolam.	2002 May	12018909
Role of GABAA/benzodiazepine receptors containing alpha 1 and alpha 5 subunits in the discriminative stimulus effects of triazolam in squirrel monkeys.	2002 May	11981598
Nighttime versus daytime hypnotic self-administration.	2002 May	11981593
Safety of zaleplon in the treatment of insomnia.	2002 May	11978165
Disposition of triazolam in the rat by brain microdialysis and semi-micro column high-performance liquid chromatography with UV absorbance detection.	2002 May	11920948
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	12297251
Interactions between recreational drugs and antiretroviral agents.	2002 Oct	12243611
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	12379159
Comparison of the effects of zaleplon, zolpidem, and triazolam at various GABA(A) receptor subtypes.	2002 Sep 13	12231378
Melatonin microinjection into the medial preoptic area increases sleep in the rat.	2002 Sep 13	12175899
Pharmacokinetic interactions with rifampicin : clinical relevance.	2003	12882588
[Cytochrome P450 3A4 and Benzodiazepines].	2003	12875231
Study of nocturnal sleep and the carryover effects of triazolam and brotizolam using neurophysiological and subjective methods.	2003	12759560
Lopinavir/ritonavir: a review of its use in the management of HIV infection.	2003	12662125
Clinical pharmacokinetic profile of modafinil.	2003	12537513
[Diagnostics and treatment of sleep disorders in elderly people].	2003 Apr-Jun	12889368
In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5.	2003 Jul	12814972
Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital.	2003 Jun	12826989
Selective effects of triazolam on memory for emotional, relative to neutral, stimuli: differential effects on gist versus detail.	2003 Jun	12802880
Role of platelet activating factor in triazolobenzodiazepines-induced retrograde amnesia.	2003 Jun 16	12798263
Differential effects in humans after repeated administrations of zolpidem and triazolam.	2003 May	12765207

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.

Name

Type

Language

N05CD05

Preferred Name

English

TRIAZOLAM

Official Name

English

TRIAZOLAM [HSDB]

Common Name

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 [WHO-DD]

Common Name

English

TRIAZOLAM [MI]

Common Name

English

U-33030

Code

English

triazolam [INN]

Common Name

English

TRIAZOLAM [USAN]

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

Common Name

English

Classification Tree Code System Code

WHO-VATC

QN05CD05