Triazolam

Identification

Summary

Triazolam is a benzodiazepine used for short term treatment of insomnia.

Brand Names
Halcion
Generic Name
Triazolam
DrugBank Accession Number
DB00897
Background

Withdrawn in the United Kingdom due to risk of psychiatric adverse drug reactions.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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 343.21
Monoisotopic: 342.043901818
Chemical Formula
C17H12Cl2N4
Synonyms
  • Triazolam
  • Triazolamum
External IDs
  • DEA No. 2887
  • N05CD05
  • U 33030

Pharmacology

Indication

For the short-term treatment of insomnia.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofInsomnia••••••••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

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.

Mechanism of action

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.

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
AGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
Absorption

Bioavailability is 44% (oral) and 53% (sublingual).

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic. Small amounts of unmetabolized triazolam appear in the urine.

Hover over products below to view reaction partners

Route of elimination

Triazolam and its metabolites, principally as conjugated glucuronides, which are presumably inactive, are excreted primarily in the urine. Only small amounts of unmetabolized triazolam appear in the urine. The two primary metabolites accounted for 79.9% of urinary excretion.

Half-life

1.5-5.5 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Symptoms of overdose include drowsiness, slurred speech, motor inco-ordination, coma, and respiratory depression.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Triazolam is combined with 1,2-Benzodiazepine.
AbacavirTriazolam may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Triazolam can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Triazolam can be increased when combined with Abatacept.
AcalabrutinibThe metabolism of Triazolam can be decreased when combined with Acalabrutinib.
Food Interactions
  • Avoid alcohol. Ingesting alcohol may increase the risk of complex behaviors like sleep-driving, which the patient does not remember.
  • Avoid grapefruit products. Grapefruit may reduce the CYP3A4 metabolism of triazolam, which increases the serum concentration of triazolam.

Products

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Product Images
International/Other Brands
Apo-Triazo (Apotex) / Arring (YungShin) / Asasion (Choseido Pharmaceutical Co., Ltd) / Ascomarna (Nisshin Seiyaku K.K) / Songar (Valeas S.p.A.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
HalcionTablet0.25 mg/1OralPharmacia & Upjohn Company LLC1982-11-15Not applicableUS flag
HalcionTablet0.125 mg/1OralPhysicians Total Care, Inc.1982-11-152012-06-30US flag
HalcionTablet0.125 mgOralPfizer Canada Ulc1980-12-312006-08-02Canada flag
HalcionTablet.125 mg/1OralPharmacia and Upjohn Company2006-01-192006-01-19US flag
HalcionTablet0.25 mgOralPfizer Canada Ulc1978-12-312007-05-29Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Alti-triazolam Tab 0.125mgTablet.125 mg / tabOralAltimed Pharma Inc.1987-12-312001-09-05Canada flag
Alti-triazolam Tab 0.25mgTablet.25 mg / tabOralAltimed Pharma Inc.1987-12-312001-09-05Canada flag
Mylan-triazolamTablet0.125 mgOralMylan Pharmaceuticals1992-12-312011-03-04Canada flag
Mylan-triazolamTablet0.25 mgOralMylan Pharmaceuticals1992-12-312011-03-04Canada flag
Novo-triolam Tab 0.125mgTablet.125 mgOralNovopharm Limited1990-12-312005-08-10Canada flag

Categories

ATC Codes
N05CD05 — Triazolam
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 1,2,4-triazolo[4,3-a][1,4]benzodiazepines. These are aromatic compounds containing a 1,4-benzodiazepine fused to and sharing a nitrogen atom with a 1,2,4-triazole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
1,4-benzodiazepines
Direct Parent
1,2,4-triazolo[4,3-a][1,4]benzodiazepines
Alternative Parents
Chlorobenzenes / Aryl chlorides / Triazoles / Heteroaromatic compounds / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
1,2,4-triazole / 1,2,4-triazolo[4,3-a][1,4]benzodiazepine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Benzenoid / Chlorobenzene / Halobenzene
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
triazolobenzodiazepine (CHEBI:9674)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
1HM943223R
CAS number
28911-01-5
InChI Key
JOFWLTCLBGQGBO-UHFFFAOYSA-N
InChI
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
IUPAC Name
12-chloro-9-(2-chlorophenyl)-3-methyl-2,4,5,8-tetraazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene
SMILES
CC1=NN=C2CN=C(C3=CC=CC=C3Cl)C3=C(C=CC(Cl)=C3)N12

References

General References
  1. Rickels K: The clinical use of hypnotics: indications for use and the need for a variety of hypnotics. Acta Psychiatr Scand Suppl. 1986;332:132-41. [Article]
  2. Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines]. Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. [Article]
  3. Noguchi H, Kitazumi K, Mori M, Shiba T: Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats. J Pharmacol Sci. 2004 Mar;94(3):246-51. [Article]
  4. Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C: Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. J Pharmacol Sci. 2007 Feb;103(2):201-6. Epub 2007 Feb 8. [Article]
  5. Veje JO, Andersen K, Gjesing S, Kielgast H: [Prescription of tranquilizers and hypnotics in the municipality of Holbaek]. Ugeskr Laeger. 1989 Aug 21;151(34):2134-6. [Article]
Human Metabolome Database
HMDB0015034
KEGG Drug
D00387
PubChem Compound
5556
PubChem Substance
46509147
ChemSpider
5355
BindingDB
50001765
RxNav
10767
ChEBI
9674
ChEMBL
CHEMBL646
ZINC
ZINC000000002212
Therapeutic Targets Database
DAP000244
PharmGKB
PA451753
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Triazolam
MSDS
Download (5.44 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedHealth Services ResearchSedation / Surgery1
3CompletedTreatmentHealthy Volunteers (HV)1
3TerminatedTreatmentAnxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia1
2CompletedTreatmentAnxiety / Pain / Sedation1
2CompletedTreatmentCocaine Related Disorders1

Pharmacoeconomics

Manufacturers
  • Pharmacia and upjohn co
  • Alphapharm party ltd
  • Roxane laboratories inc
  • Watson laboratories inc
Packagers
  • Alphapharm Party Ltd.
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • Corepharma LLC
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Genpharm LP
  • Greenstone LLC
  • H.J. Harkins Co. Inc.
  • Keltman Pharmaceuticals Inc.
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Pharmacia Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Roxane Labs
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
Dosage Forms
FormRouteStrength
TabletOral.125 mg / tab
TabletOral.25 mg / tab
TabletOral.125 mg/1
TabletOral125 MICROGRAMMI
TabletOral250 MICROGRAMMI
TabletOral
TabletOral0.125 mg
TabletOral.125 mg
TabletOral.25 mg
Capsule
Solution / dropsOral
TabletOral0.1250 mg
TabletOral0.125 mg/1
TabletOral0.25 mg
TabletOral0.25 mg/1
TabletOral0125 MG
Prices
Unit descriptionCostUnit
Halcion 10 0.25 mg tablet Bottle21.0USD bottle
Triazolam 10 0.125 mg tablet Bottle6.33USD bottle
Triazolam 10 0.25 mg tablet Bottle6.0USD bottle
Halcion 0.25 mg tablet1.99USD tablet
Halcion 0.125 mg tablet1.37USD tablet
Triazolam 0.25 mg tablet0.67USD tablet
Triazolam 0.125 mg tablet0.65USD tablet
Apo-Triazo 0.25 mg Tablet0.22USD tablet
Mylan-Triazolam 0.25 mg Tablet0.22USD tablet
Apo-Triazo 0.125 mg Tablet0.12USD tablet
Mylan-Triazolam 0.125 mg Tablet0.12USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)233-235 °CNot Available
water solubility4.53 mg/LNot Available
logP2.42BIOBYTE (1995)
logS-4.08ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0183 mg/mLALOGPS
logP2.94ALOGPS
logP3.63Chemaxon
logS-4.3ALOGPS
pKa (Strongest Acidic)17.98Chemaxon
pKa (Strongest Basic)4.26Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area43.07 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity103.68 m3·mol-1Chemaxon
Polarizability34.19 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9719
Caco-2 permeable+0.886
P-glycoprotein substrateNon-substrate0.5252
P-glycoprotein inhibitor INon-inhibitor0.6788
P-glycoprotein inhibitor IIInhibitor0.8331
Renal organic cation transporterInhibitor0.7628
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9208
CYP450 3A4 substrateSubstrate0.751
CYP450 1A2 substrateInhibitor0.8598
CYP450 2C9 inhibitorInhibitor0.815
CYP450 2D6 inhibitorNon-inhibitor0.8226
CYP450 2C19 inhibitorInhibitor0.7117
CYP450 3A4 inhibitorNon-inhibitor0.5596
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9088
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.6714
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9971 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9638
hERG inhibition (predictor II)Non-inhibitor0.8806
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0006-8089000000-80a2c04b55ba4ec57f7d
Mass Spectrum (Electron Ionization)MSsplash10-0imr-4954000000-75bcea16a1182103168f
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-439a372277eb9d7b84c5
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-9a1a20ce1a0982eb608a
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-ba834846753af69ac024
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-c2d9a1315e70661774c4
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01ri-0096000000-e7da2771e1cfa7c211eb
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0f9x-3192000000-a6123eaa7899f05d0158
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-174.3785356
predicted
DarkChem Lite v0.1.0
[M-H]-171.45076
predicted
DeepCCS 1.0 (2019)
[M+H]+175.0905356
predicted
DarkChem Lite v0.1.0
[M+H]+173.80876
predicted
DeepCCS 1.0 (2019)
[M+Na]+174.9081356
predicted
DarkChem Lite v0.1.0
[M+Na]+180.69753
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
  2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
Curator comments
Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
  2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. [Article]
  2. Schrag ML, Wienkers LC: Triazolam substrate inhibition: evidence of competition for heme-bound reactive oxygen within the CYP3A4 active site. Drug Metab Dispos. 2001 Jan;29(1):70-5. [Article]
  3. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
This enzyme relationship is supported by 1 in vitro study available in the literature.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Ong CE, Coulter S, Birkett DJ, Bhasker CR, Miners JO: The xenobiotic inhibitor profile of cytochrome P4502C8. Br J Clin Pharmacol. 2000 Dec;50(6):573-80. doi: 10.1046/j.1365-2125.2000.00316.x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Patki KC, Von Moltke LL, Greenblatt DJ: In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Drug Metab Dispos. 2003 Jul;31(7):938-44. [Article]
  2. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. [Article]
  3. Flockhart Table of Drug Interactions [Link]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48