| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-06-23 18:08:07 |
| Primary Accession Number |
DB00897 |
| Secondary Accession Number |
|
| Name |
Triazolam |
| Drug Type |
- Approved
- Illicit
- Small Molecule
- Withdrawn
|
| 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Withdrawn in the United Kingdom due to risk of psychiatric adverse drug reactions.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. |
| Synonyms |
- DEA No. 2887
- Triazolamum [INN-Latin]
|
| Brand Names |
- Alti-Triazolam
- Apo-Triazo
- Clorazolam
- Gen-Triazolam
- Halcion
- Novidorm
- Novo-Triolam
- Novodorm
- Songar
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
8-chloro-6-(2-chlorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine |
| Chemical Formula |
C17H12Cl2N4 |
| Chemical Structure |
 |
| CAS Registry Number |
28911-01-5 |
| InChI Identifier |
InChI=1/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 |
| InChI Key |
JOFWLTCLBGQGBO-UHFFFAOYAU |
| KEGG Drug |
D00387  |
| KEGG Compound |
Not Available |
| PubChem Compound |
5556  |
| PubChem Substance |
7847453  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA451753  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02230024  |
| RxList Link |
http://www.rxlist.com/cgi/generic/triazolam.htm  |
| PDRhealth Link |
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/hal1192.shtml  |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Triazolam  |
| FDA Label |
Not Available |
| Material Safety Data Sheet (MSDS) |
|
| Synthesis Reference |
J. B. Hester, U.S. Pat. 3,701,782 (1972) |
| Average Molecular Weight |
343.2100 |
| Monoisotopic Molecular Weight |
342.0439 |
| State |
Solid |
| Melting Point |
233-235 oC |
| Experimental Water Solubility |
4.53 mg/L
Source: PhysProp
|
| Predicted Water Solubility |
1.83e-02 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
5.5
Source: PhysProp
|
| Predicted LogP |
2.94
Calculated using ALOGPS
|
| Experimental LogS |
-4.08 [ADME Research, USCD] |
| Predicted LogS |
-4.27
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
Not Available |
| Isomeric SMILES |
CC1=NN=C2CN=C(C3=CC=CC=C3Cl)C3=C(C=CC(Cl)=C3)N12 |
| Canonical SMILES |
CC1=NN=C2CN=C(C3=CC=CC=C3Cl)C3=C(C=CC(Cl)=C3)N12 |
| Drug Category |
- Adjuvants, Anesthesia
- Anti-anxiety Agents
- Benzodiazepines
- GABA Modulators
|
| ATC Codes |
|
| AHFS Codes |
|
| Indication |
For the short-term treatment of insomnia. |
| Pharmacology |
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. |
| Absorption |
Bioavailability is 44% (oral) and 53% (sublingual). |
| Toxicity |
Symptoms of overdose include drowsiness, slurred speech, motor inco-ordination, coma, and respiratory depression. |
| Protein Binding |
Not Available |
| Biotransformation |
Hepatic. Small amounts of unmetabolized triazolam appear in the urine. |
| Half Life |
1.5-5.5 hours |
| Dosage Forms |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
| Drug |
Interaction |
| Amprenavir |
Amprenavir increases the effect and toxicity of benzodiazepine |
| Aprepitant |
Aprepitant increases the effect and toxicity of benzodiazepine |
| Atazanavir |
Atazanavir increases the effect and toxicity of benzodiazepine |
| Cimetidine |
Cimetidine increases the effect and toxicity of benzodiazepine |
| Clarithromycin |
The macrolide increases the effect of the benzodiazepine |
| Clozapine |
Increased risk of toxicity |
| Delavirdine |
The antiviral agent increases the effect and toxicity of benzodiazepine |
| Diltiazem |
The calcium channel blocker increases the effect and toxicity of the benzodiazepine |
| Efavirenz |
The antiviral agent increases the effect and toxicity of benzodiazepine |
| Erythromycin |
The macrolide increases the effect of the benzodiazepine |
| Ethotoin |
Possible increased levels of the hydantoin, decrease of benzodiazepine |
| Fluconazole |
Fluconazole increases the effect of the benzodiazepine |
| Fosamprenavir |
Amprenavir increases the effect and toxicity of benzodiazepine |
| Fosphenytoin |
Possible increased levels of the hydantoin, decrease of benzodiazepine |
| Indinavir |
The protease inhibitor increases the effect of the benzodiazepine |
| Itraconazole |
The imidazole increases the effect of the benzodiazepine |
| Josamycin |
The macrolide increases the effect of the benzodiazepine |
| Kava |
Kava increases the effect of the benzodiazepine |
| Ketoconazole |
The imidazole increases the effect of the benzodiazepine |
| Mephenytoin |
Possible increased levels of the hydantoin, decrease of benzodiazepine |
| Modafinil |
Modafinil decreases the effect of triazolam |
| Nefazodone |
Nefazodone increases the effect of triazolam |
| Nelfinavir |
The protease inhibitor increases the effect of the benzodiazepine |
| Omeprazole |
Omeprazole increases the effect of the benzodiazepine |
| Phenytoin |
Possible increased levels of the hydantoin, decrease of benzodiazepine |
| Rifampin |
Rifampin decreases the effect of the benzodiazepine |
| Ritonavir |
The protease inhibitor increases the effect of the benzodiazepine |
| Saquinavir |
The protease inhibitor increases the effect of the benzodiazepine |
| St. John's Wort |
St. John's Wort could reduce the benzodiazepine effect |
| Telithromycin |
Telithromycin increases the effect/toxicity of the benzodiazepine |
| Verapamil |
The calcium channel blocker increases the effect and toxicity of the benzodiazepine |
| Voriconazole |
The imidazole increases the effect of the benzodiazepine |
|
| Food Interactions |
Not Available
|
| Pathways |
Not Available
|
| General References |
- 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. [PubMed
]
- 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. [PubMed
]
- Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines] Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. [PubMed
]
- 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. [PubMed
]
- 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. [PubMed
]
- Drugs.com

- Wikipedia

- RxList

- PDRhealth

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 3A4 (CYP3A4)
|
| Targets |
- Translocator protein
|
|
Drug Target 1
[top]
|
| Target 1 ID |
811 |
| Target 1 Name |
Translocator protein |
| Target 1 Synonyms |
- Mitochondrial benzodiazepine receptor
- PBR
- PKBS
- Peripheral-type benzodiazepine receptor
|
| Target 1 Gene Name |
BZRP |
| Target 1 Protein Sequence |
>Peripheral-type benzodiazepine receptor
MAPPWVPAMGFTLAPSLGCFVGSRFVHGEGLRWYAGLQKPSWHPPHWVLGPVWGTLYSAM
GYGSYLVWKELGGFTEKAVVPLGLYTGQLALNWAWPPIFFGARQMGWALVDLLLVSGAAA
ATTVAWYQVSPLAARLLYPYLAWLAFATTLNYCVWRDNHGWHGGRRLPE
|
| Target 1 Number of Residues |
171 |
| Target 1 Molecular Weight |
18779 |
| Target 1 Theoretical pI |
9.33 |
| Target 1 GO Classification |
|
Function
|
| Not Available |
|
Process
|
| Not Available |
|
Component
|
cell
membrane
intrinsic to membrane
integral to membrane |
|
| Target 1 General Function |
Signal transduction mechanisms |
| Target 1 Specific Function |
Responsible for the manifestation of peripheral-type benzodiazepine recognition sites and is most likely to comprise binding domains for benzodiazepines and isoquinoline carboxamides. May play a role in the transport of porphyrins and heme |
| Target 1 Pathways |
Not Available
|
| Target 1 Reactions |
Not Available |
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
- 6-26
- 47-67
- 80-100
- 106-126
- 135-155
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
306883  |
| Target 1 UniProtKB/Swiss-Prot ID |
P30536  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
BZRP_HUMAN  |
| Target 1 PDB ID |
Not Available |
| Target 1 Cellular Location |
- Mitochondrion
- mitochondrial membrane
- multi-pass membrane protein
|
| Target 1 Gene Sequence |
>510 bp
ATGGCCCCGCCCTGGGTGCCCGCCATGGGCTTCACGCTGGCGCCCAGCCTGGGGTGCTTC
GTGGGCTCCCGCTTTGTCCACGGCGAGGGTCTCCGCTGGTACGCCGGCCTGCAGAAGCCC
TCGTGGCACCCGCCCCACTGGGTGCTGGGCCCTGTCTGGGGCACGCTCTACTCAGCCATG
GGGTACGGCTCCTACCTGGTCTGGAAAGAGCTGGGAGGCTTCACAGAGAAGGCTGTGGTT
CCCCTGGGCCTCTACACTGGGCAGCTGGCCCTGAACTGGGCATGGCCCCCCATCTTCTTT
GGTGCCCGACAAATGGGCTGGGCCTTGGTGGATCTCCTGCTGGTCAGTGGGGCGGCGGCN
GCCACTACCGTGGCCTGGTACCAGGTGAGCCCGCTGGCCGCCCGCCTGCTCTACCCCTAC
CTGGCCTGGCTGGCCTTCGCGACCACACTCAACTACTGCGTATGGCGGGACAACCATGGC
TGGCATGGGGGACGGCGGCTGCCAGAGTGA
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
TSPO  |
| Target 1 GenAtlas ID |
TSPO  |
| Target 1 HGNC ID |
HGNC:1158  |
| Target 1 Chromosome Location |
22 |
| Target 1 Locus |
22q13.31 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [PubMed
]
- Kurumaji A, Nomoto H, Yoshikawa T, Okubo Y, Toru M: An association study between two missense variations of the benzodiazepine receptor (peripheral) gene and schizophrenia in a Japanese sample. J Neural Transm. 2000;107(4):491-500. [PubMed
]
- Kurumaji A, Nomoto H, Yamada K, Yoshikawa T, Toru M: No association of two missense variations of the benzodiazepine receptor (peripheral) gene and mood disorders in a Japanese sample. Am J Med Genet. 2001 Mar 8;105(2):172-5. [PubMed
]
- Riond J, Mattei MG, Kaghad M, Dumont X, Guillemot JC, Le Fur G, Caput D, Ferrara P: Molecular cloning and chromosomal localization of a human peripheral-type benzodiazepine receptor. Eur J Biochem. 1991 Jan 30;195(2):305-11. [PubMed
]
- Yakovlev AG, Ruffo M, Jurka J, Krueger KE: Comparison of repetitive elements in the third intron of human and rodent mitochondrial benzodiazepine receptor-encoding genes. Gene. 1995 Apr 3;155(2):201-5. [PubMed
]
- Galiegue S, Jbilo O, Combes T, Bribes E, Carayon P, Le Fur G, Casellas P: Cloning and characterization of PRAX-1. A new protein that specifically interacts with the peripheral benzodiazepine receptor. J Biol Chem. 1999 Jan 29;274(5):2938-52. [PubMed
]
|
| Target 1 Drug References |
- Park CH, Carboni E, Wood PL, Gee KW: Characterization of peripheral benzodiazepine type sites in a cultured murine BV-2 microglial cell line. Glia. 1996 Jan;16(1):65-70. [PubMed
]
|