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Compound Detail

CHEMBL646

TRIAZOLAM
💊 Approved Drug
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💊 Approved Drug
Cc1nnc2n1-c1ccc(Cl)cc1C(c1ccccc1Cl)=NC2

Basic Information

ChEMBL ID CHEMBL646
Name TRIAZOLAM
Phase Approved
Structure Type MOL
InChI Key JOFWLTCLBGQGBO-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Halcion Kention N05CD05 Triazolam Triazolam civ U-33,030 U-33030
11
Targets
14
Activities
4
Assay Types
12
PK Parameters
20
Publications
7
Known Names
6
Indications
1
Mechanisms

Molecular Properties

343.2
MW (Da)
4.23
ALogP
4
HBA
0
HBD
43.1
PSA (Ų)
0.66
QED
0
Ro5 Violations
1
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1978
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Black Box Warning Withdrawn Natural Product
USAN Year 1973

Extended Properties

Molecular Formula C17H12Cl2N4
MW 343.22
Aromatic Rings 3
Heavy Atoms 23
NP-Likeness -0.87

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
GABA-A receptor; anion channel positive allosteric modulator POSITIVE ALLOSTERIC MODULATOR GABA-A receptor; anion channel

Indications

Sleep Initiation and Maintenance Disorders Anxiety Dementia Depressive Disorder Schizophrenia Substance-Related Disorders

ATC Classification

N05CD05
triazolam
Level 1: NERVOUS SYSTEM
Level 2: PSYCHOLEPTICS

Drug Warnings

Withdrawn
neurotoxicity
Psychiatric reaction and amnesia
Country: France; United Kingdom; Argentina; Finland; Netherlands   Year: 1982
Withdrawn
psychiatric toxicity
Psychiatric reaction and amnesia
Country: France; United Kingdom; Argentina; Finland; Netherlands   Year: 1982
Withdrawn
psychiatric toxicity
serious psychiatric adverse effects, including memory disturbances, anxiety, depression and agressivity
Country: Norway   Year: 1982
Withdrawn
psychiatric toxicity
serious psychiatric adverse effects, including memory disturbances, anxiety, depression and agressivity
Country: Norway   Year: 1982
Withdrawn
neurotoxicity
psychiatric adverse effects, particularly loss of memory and depression
Country: France; United Kingdom; Argentina; Finland; Netherlands   Year: 1982
Withdrawn
psychiatric toxicity
serious psychiatric adverse effects, including memory disturbances, anxiety, depression and agressivity
Country: Norway   Year: 1982
Withdrawn
psychiatric toxicity
psychiatric adverse effects, particularly loss of memory and depression
Country: France; United Kingdom; Argentina; Finland; Netherlands   Year: 1982
Withdrawn
General Warning
harmful
Country: Mauritius   Year: 1982
Withdrawn
psychiatric toxicity
serious psychiatric adverse effects, including memory disturbances, anxiety, depression and agressivity
Country: Norway   Year: 1982
Black Box Warning
General Warning
Country: United States

Activity Summary

Ki 6 meas. best 9.23
IC50 5 meas. best 8.81
Kd 2 meas. best 9.0
EC50 1 meas. best 7.66

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
GABA-A receptor; alpha-2/beta-3/gamma-2
CHEMBL2094130
Ki 9.23 9.23 0.6 1
GABA-A receptor; anion channel
CHEMBL1907607
Ki 9.1 7.39 0.8 2
GABA-A receptor; alpha-1/beta-3/gamma-2
CHEMBL2094121
Ki 9.1 9.1 0.8 1
Gamma-aminobutyric acid receptor subunit alpha-1
CHEMBL1962
Kd 9.0 9.0 1.0 1
GABA-A receptor; alpha-3/beta-3/gamma-2
CHEMBL2094120
Ki 8.85 8.85 1.4 1
GABA-A receptor; alpha-5/beta-3/gamma-2
CHEMBL2094122
Ki 8.81 8.81 1.5 1
Unchecked
CHEMBL612545
IC50 8.81 8.81 1.5 1
Gamma-aminobutyric acid receptor subunit alpha-5
CHEMBL5112
Kd 8.4 8.4 4.0 1
Unchecked
CHEMBL612545
EC50 7.66 7.66 22.0 1
Oryctolagus cuniculus
CHEMBL374
IC50 4.96 4.96 11100.0 2
Platelet-activating factor receptor
CHEMBL5136
IC50 4.96 4.96 11100.0 1
Cholecystokinin receptor type A
CHEMBL2871
IC50 4.41 4.41 39000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 3.0 mL.min-1.kg-1 Homo sapiens
CL 2.9 mL.min-1.kg-1 Homo sapiens
CL 3.0 mL.min-1.kg-1 Homo sapiens
CL 3.0 mL.min-1.kg-1 Homo sapiens
CL 150.0 uL.min-1.(10^6cells)-1 Rattus norvegicus
F 49.0 % Homo sapiens
F 44.0 % Homo sapiens
Fu 0.1 - Homo sapiens
Fu 0.1 - Homo sapiens
Fu 0.1 - Homo sapiens
MRT 3.2 hr Homo sapiens
T1/2 2.7 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
GABA-A receptor; alpha-2/beta-3/gamma-2 Ki = 0.59 nM 9.23 Binding affinity to human recombinant gamma-aminobutyric-acid (GABA) A receptor ... 10633039
GABA-A receptor; alpha-1/beta-3/gamma-2 Ki = 0.8 nM 9.1 Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor... 10633039
GABA-A receptor; anion channel Ki = 0.8 nM 9.1 Binding affinity for Diazepam sensitive (DS) isoform of the benzodiazepine (Bz) ... 8390574
Gamma-aminobutyric acid receptor subunit alpha-1 Kd = 1.0 nM 9.0 Binding affinity to GABAA alpha-1-beta-2-gamma-2 receptor 18537233
GABA-A receptor; alpha-3/beta-3/gamma-2 Ki = 1.43 nM 8.85 Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor... 10633039
Unchecked IC50 = 1.54 nM 8.81 Displacement of [3H]flunitrazepam from GABAA benzodiazepine receptor in rat brai... 18829330
GABA-A receptor; alpha-5/beta-3/gamma-2 Ki = 1.54 nM 8.81 Binding affinity for human recombinant gamma-aminobutyric-acid (GABA) A receptor... 10633039
Gamma-aminobutyric acid receptor subunit alpha-5 Kd = 4.0 nM 8.4 Binding affinity to GABAA alpha-5-beta-2-gamma-2 receptor 18537233
Unchecked EC50 = 22.0 nM 7.66 Allosteric modulation of gamma-aminobutyric acid receptor A alpha1beta2gamma2S e... 21793559
GABA-A receptor; anion channel Ki = 2086.0 nM 5.68 Binding affinity for Diazepam insensitive (DI) isoform of the benzodiazepine (Bz... 8390574
Oryctolagus cuniculus IC50 = 11100.0 nM 4.96 Concentration required to inhibit PAF (5*10e-8 M) induced platelet aggregation i... 1336052
Platelet-activating factor receptor IC50 = 11100.0 nM 4.96 Inhibition of PAF-induced platelet aggregation in rabbit platelet rich plasma 8496938
Oryctolagus cuniculus IC50 = 11100.0 nM 4.96 Concentration needed to inhibit PAF-induced platelet aggregation in rabbit PRP b... 1578493
Cholecystokinin receptor type A IC50 = 39000.0 nM 4.41 Displacement of [125I]CCK from Cholecystokinin receptor of rat pancreas 3336017

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885861 Rattus norvegicus 1376
16472241 10.2174/1570163043334794 Hepatotoxicity 18
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
31483 10.1021/jm00210a022 Mus musculus 11
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
42799 10.1021/jm00197a021 Mus musculus 10
9511 10.1021/jm00230a016 Mus musculus 9
27634 10.1021/jm00204a008 Mus musculus 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
22301272 10.1124/dmd.111.041681 Liver microsome 8
22301272 10.1124/dmd.111.041681 Cytochrome P450 3A4 8
20070106 10.1021/jm901371v Homo sapiens 8
7154007 10.1021/jm00354a015 Mus musculus 6
18426954 10.1124/dmd.108.020479 ADMET 4
27634 10.1021/jm00204a008 Brain 3
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 3
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2A 3
8390574 10.1021/jm00065a004 GABA-A receptor; anion channel 3
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 1A 3
30093345 10.1016/j.bmc.2018.08.002 Mus musculus 3

Data from ChEMBL 36 via Core Engine