Triazolam

Synonyms :
Halcion, Triazolam, Triazolam, Triazolam, Triazolamum

Status : approved

Category

Anti-Anxiety Agents

Therapeutic Classification

HYPNOTICS AND SEDATIVES

NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Adjuvants, Anesthesia

Description

Withdrawn in the United Kingdom due to risk of psychiatric adverse drug reactions.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

Used

For the short-term treatment of insomnia.

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.

Dosage

Form Route Strength
Tablet oral .25 mg
Tablet oral 0.125 mg
Tablet oral .125 mg
Tablet oral 0.25 mg

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.

Toxic Effect

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

Metabolism

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

Absorption

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

Half Life

1.5-5.5 hours

Elimination Route

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.

Chemical Classification

This compound belongs to the class of organic compounds known as 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.

1,4-benzodiazepines

Organic compounds

Organoheterocyclic compounds

Benzodiazepines

1,4-benzodiazepines

Chemical Name

Halcion

Brands

name Dosage form Country
Alti-triazolam Tab 0.125mg tablet Canada
Alti-triazolam Tab 0.25mg tablet Canada
Halcion tablet US
Halcion tablet Canada
Halcion tablet Canada
Mylan-triazolam tablet Canada
Mylan-triazolam tablet Canada
Novo-triolam Tab 0.125mg tablet Canada
Novo-triolam Tab 0.25mg tablet Canada
Penta-triazolam Tablets tablet Canada
Penta-triazolam Tablets tablet Canada
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam tablet Canada
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam tablet Canada
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam tablet US
Triazolam Tab 0.125mg tablet Canada
Triazolam Tab 0.25mg tablet Canada
Triazolam Tablets 0.125mg tablet Canada
Triazolam Tablets 0.25mg tablet Canada

Drug Drug Interactions

  •  Aminophylline  : Theophylline Derivatives may diminish the therapeutic effect of Benzodiazepines.
  •  Amodiaquine  : CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine.
  •  Aprepitant  : May increase the serum concentration of CYP3A4 Substrates.
  •  Atazanavir  : Protease Inhibitors may increase the serum concentration of Triazolam.
  •  Batimastat  : May increase the serum concentration of Triazolam.
  •  Boceprevir  : May increase the serum concentration of Triazolam.
  •  Bosentan  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Buprenorphine  : CNS Depressants may enhance the CNS depressant effect of Buprenorphine.
  •  Clarithromycin  : Macrolide Antibiotics may increase the serum concentration of Triazolam.
  •  Clozapine  : Benzodiazepines may enhance the adverse/toxic effect of Clozapine.
  •  Cobicistat  : May increase the serum concentration of Triazolam.
  •  Conivaptan  : May increase the serum concentration of CYP3A4 Substrates.
  •  Dabrafenib  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Darunavir  : Protease Inhibitors may increase the serum concentration of Triazolam.
  •  Dasatinib  : May increase the serum concentration of CYP3A4 Substrates.
  •  Deferasirox  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Dexamethasone  : Dexamethasone (Systemic) may decrease the serum concentration of Triazolam.
  •  Doxylamine  : May enhance the CNS depressant effect of CNS Depressants.
  •  Dronabinol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Dronabinol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Droperidol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Dyphylline  : Theophylline Derivatives may diminish the therapeutic effect of Benzodiazepines.
  •  Erythromycin  : Macrolide Antibiotics may increase the serum concentration of Triazolam.
  •  Fosamprenavir  : Protease Inhibitors may increase the serum concentration of Triazolam.
  •  Fosaprepitant  : May increase the serum concentration of CYP3A4 Substrates.
  •  Fosphenytoin  : May increase the serum concentration of Fosphenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Gamma Hydroxybutyric Acid  : May enhance the CNS depressant effect of Sodium Oxybate.
  •  Hydrocodone  : CNS Depressants may enhance the CNS depressant effect of Hydrocodone.
  •  Hydroxyzine  : May enhance the CNS depressant effect of CNS Depressants.
  •  Idelalisib  : May increase the serum concentration of CYP3A4 Substrates.
  •  Indinavir  : Protease Inhibitors may increase the serum concentration of Triazolam.
  •  Isoflurophate  : May increase the serum concentration of Triazolam.
  •  Itraconazole  : May increase the serum concentration of Triazolam.
  •  Ivacaftor  : May increase the serum concentration of CYP3A4 Substrates.
  •  Ketoconazole  : Ketoconazole (Systemic) may increase the serum concentration of Triazolam.
  •  Lopinavir  : Protease Inhibitors may increase the serum concentration of Triazolam.
  •  Luliconazole  : May increase the serum concentration of CYP3A4 Substrates.
  •  Magnesium Sulfate  : May enhance the CNS depressant effect of CNS Depressants.
  •  Methadone  : Benzodiazepines may enhance the CNS depressant effect of Methadone.
  •  Methotrimeprazine  : CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants.
  •  Metyrosine  : CNS Depressants may enhance the sedative effect of Metyrosine.
  •  Mifepristone  : May increase the serum concentration of CYP3A4 Substrates.
  •  Minocycline  : May enhance the CNS depressant effect of CNS Depressants.
  •  Mirtazapine  : CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
  •  Mitotane  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Nabilone  : May enhance the CNS depressant effect of CNS Depressants.
  •  Nelfinavir  : Protease Inhibitors may increase the serum concentration of Triazolam.
  •  Netupitant  : May increase the serum concentration of CYP3A4 Substrates.
  •  Olanzapine  : May enhance the adverse/toxic effect of Benzodiazepines.
  •  Orphenadrine  : CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
  •  Palbociclib  : May increase the serum concentration of CYP3A4 Substrates.
  •  Paraldehyde  : CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
  •  Perampanel  : May enhance the CNS depressant effect of CNS Depressants.
  •  Phenytoin  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Pramipexole  : CNS Depressants may enhance the sedative effect of Pramipexole.
  •  Ritonavir  : Protease Inhibitors may increase the serum concentration of Triazolam.
  •  Ropinirole  : CNS Depressants may enhance the sedative effect of Ropinirole.
  •  Rotigotine  : CNS Depressants may enhance the sedative effect of Rotigotine.
  •  Rufinamide  : May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
  •  Saquinavir  : Protease Inhibitors may increase the serum concentration of Triazolam.
  •  Siltuximab  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Simeprevir  : May increase the serum concentration of Triazolam.
  •  Sodium oxybate  : Benzodiazepines may enhance the CNS depressant effect of Sodium oxybate.
  •  Stiripentol  : May increase the serum concentration of CYP3A4 Substrates.
  •  Sulfisoxazole  : Macrolide Antibiotics may increase the serum concentration of Triazolam.
  •  Suvorexant  : CNS Depressants may enhance the CNS depressant effect of Suvorexant.
  •  Tapentadol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Teduglutide  : May increase the serum concentration of Benzodiazepines.
  •  Telaprevir  : May increase the serum concentration of Triazolam.
  •  Telithromycin  : Macrolide Antibiotics may increase the serum concentration of Triazolam.
  •  Thalidomide  : CNS Depressants may enhance the CNS depressant effect of Thalidomide.
  •  Theophylline  : Theophylline Derivatives may diminish the therapeutic effect of Benzodiazepines.
  •  Tipranavir  : Protease Inhibitors may increase the serum concentration of Triazolam.
  •  Tocilizumab  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Yohimbine  : May diminish the therapeutic effect of Antianxiety Agents.
  •  Zolpidem  : CNS Depressants may enhance the CNS depressant effect of Zolpidem.

Calculated Property

kind Value Source
logP 2.94 ALOGPS
logS -4.3 ALOGPS
Water Solubility 1.83e-02 g/l ALOGPS
logP 2.89 ChemAxon
IUPAC Name 12-chloro-9-(2-chlorophenyl)-3-methyl-2,4,5,8-tetraazatricyclo[8.4.0.0²,⁶]tetradeca-1(10),3,5,8,11,13-hexaene ChemAxon
Traditional IUPAC Name triazolam ChemAxon
Molecular Weight 343.21 ChemAxon
Monoisotopic Weight 342.043901818 ChemAxon
SMILES CC1=NN=C2CN=C(C3=CC=CC=C3Cl)C3=C(C=CC(Cl)=C3)N12 ChemAxon
Molecular Formula C17H12Cl2N4 ChemAxon
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 ChemAxon
InChIKey InChIKey=JOFWLTCLBGQGBO-UHFFFAOYSA-N ChemAxon
Polar Surface Area (PSA) 43.07 ChemAxon
Refractivity 103.68 ChemAxon
Polarizability 34.19 ChemAxon
Rotatable Bond Count 1 ChemAxon
H Bond Acceptor Count 3 ChemAxon
H Bond Donor Count 0 ChemAxon
pKa (strongest acidic) 18.08 ChemAxon
pKa (strongest basic) 4.32 ChemAxon
Physiological Charge 0 ChemAxon
Number of Rings 4 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Gamma-aminobutyric acid receptor subunit alpha-1 : in Human
  • Gamma-aminobutyric acid receptor subunit alpha-2 : in Human
  • Gamma-aminobutyric acid receptor subunit alpha-3 : in Human
  • Gamma-aminobutyric acid receptor subunit alpha-4 : in Human
  • Gamma-aminobutyric acid receptor subunit alpha-5 : in Human
  • Gamma-aminobutyric acid receptor subunit alpha-6 : in Human
  • Gamma-aminobutyric acid receptor subunit beta-1 : in Human
  • Gamma-aminobutyric acid receptor subunit beta-2 : in Human
  • Gamma-aminobutyric acid receptor subunit beta-3 : in Human
  • Gamma-aminobutyric acid receptor subunit gamma-1 : in Human
  • Gamma-aminobutyric acid receptor subunit gamma-2 : in Human
  • Gamma-aminobutyric acid receptor subunit gamma-3 : in Human
  • Gamma-aminobutyric acid receptor subunit delta : in Human
  • Gamma-aminobutyric acid receptor subunit epsilon : in Human
  • Gamma-aminobutyric acid receptor subunit pi : in Human
  • Gamma-aminobutyric acid receptor subunit rho-1 : in Human
  • Gamma-aminobutyric acid receptor subunit rho-2 : in Human
  • Gamma-aminobutyric acid receptor subunit rho-3 : in Human
  • Gamma-aminobutyric acid receptor subunit theta : in Human
  • Translocator protein : in Human
  • GABA-A receptor (anion channel) : in Human