Details
Stereochemistry | ACHIRAL |
Molecular Formula | C16H13ClN2O.ClH |
Molecular Weight | 321.201 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CN1C2=CC=C(Cl)C=C2C(=NCC1=O)C3=CC=CC=C3
InChI
InChIKey=BPYZIOINRAWEQL-UHFFFAOYSA-N
InChI=1S/C16H13ClN2O.ClH/c1-19-14-8-7-12(17)9-13(14)16(18-10-15(19)20)11-5-3-2-4-6-11;/h2-9H,10H2,1H3;1H
DescriptionCurator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24552479
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24552479
Diazepam is a benzodiazepine first discovered at Hoffman-La Roche in the late 1950s. Diazepam was approved by FDA for the treatment of anxiety disorders as well as for such conditions as skeletal muscle spasm, alcohol withdrawal syndrom and convulsions (under the most known brand Valium). The drug acts by binding to GABA-A receptors and potentiating GABA evoked current. Chronic diazepam use is associated with tolerance, dependence, and withdrawal.
CNS Activity
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24007886
Curator's Comment: # Hoffmann-La Roche
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2109243 |
8.6 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | VALIUM Approved UseValium is indicated for the management of anxiety disorders or for the shortterm relief of the symptoms of anxiety. In acute alcohol withdrawal, Valium may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. Valium is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma), spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia), athetosis, and stiff-man syndrome. Oral Valium may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy. Launch Date1963 |
|||
Palliative | VALIUM Approved UseValium is indicated for the management of anxiety disorders or for the shortterm relief of the symptoms of anxiety. In acute alcohol withdrawal, Valium may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. Valium is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma), spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia), athetosis, and stiff-man syndrome. Oral Valium may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy. Launch Date1963 |
|||
Palliative | VALIUM Approved UseValium is indicated for the management of anxiety disorders or for the shortterm relief of the symptoms of anxiety. In acute alcohol withdrawal, Valium may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. Valium is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma), spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia), athetosis, and stiff-man syndrome. Oral Valium may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy. Launch Date1963 |
|||
Palliative | VALIUM Approved UseValium is indicated for the management of anxiety disorders or for the shortterm relief of the symptoms of anxiety. In acute alcohol withdrawal, Valium may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. Valium is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma), spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia), athetosis, and stiff-man syndrome. Oral Valium may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy. Launch Date1963 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
317 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1505149 |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
DIAZEPAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
75 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1505149 |
2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered: |
DIAZEPAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
172 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1505149 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
DIAZEPAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
208 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01417078 |
20 mg single, intranasal dose: 20 mg route of administration: intranasal experiment type: single co-administered: |
DIAZEPAM plasma | Homo sapiens population: unhealthy age: sex: food status: |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1530 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1505149 |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
DIAZEPAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
330 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1505149 |
2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered: |
DIAZEPAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
779 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1505149 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
DIAZEPAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1227 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01417078 |
20 mg single, intranasal dose: 20 mg route of administration: intranasal experiment type: single co-administered: |
DIAZEPAM plasma | Homo sapiens population: unhealthy age: sex: food status: |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
48 h |
unknown, oral |
DIAZEPAM plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2% |
unknown, oral |
DIAZEPAM plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
2000 mg single, oral Overdose |
healthy, 28 years |
|
500 mg single, oral Overdose |
unhealthy, 61 years |
|
0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Sources: |
Other AEs: Respiratory depression, Abuse... Other AEs: Respiratory depression (serious|grade 5) Sources: Abuse (serious|grade 5) |
0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years n = 573 Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Population Size: 573 Sources: |
Disc. AE: Somnolence, Hypoventilation... AEs leading to discontinuation/dose reduction: Somnolence (3 patients) Sources: Hypoventilation (2 patients) Rash (2 patients) Asthenia (1 patient) Hyperkinesia (1 patient) Incoordination (1 patient) Vasodilatation (1 patient) Urticaria (1 patient) |
10 mg 2 times / day multiple, intranasal Recommended Dose: 10 mg, 2 times / day Route: intranasal Route: multiple Dose: 10 mg, 2 times / day Co-administed with:: benzodiazepines Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Respiratory depression... Other AEs: Respiratory depression (serious|grade 5) Sources: |
10 mg 4 times / day multiple, intramuscular Recommended Dose: 10 mg, 4 times / day Route: intramuscular Route: multiple Dose: 10 mg, 4 times / day Co-administed with:: benzodiazepines Sources: |
unhealthy, adult Health Status: unhealthy Condition: anxiety disorders Age Group: adult Sources: |
Other AEs: Respiratory depression, Abuse... Other AEs: Respiratory depression (serious|grade 5) Sources: Abuse (serious|grade 5) |
10 mg 4 times / day multiple, oral Recommended Dose: 10 mg, 4 times / day Route: oral Route: multiple Dose: 10 mg, 4 times / day Co-administed with:: OPIOIDS Sources: |
unhealthy, adult Health Status: unhealthy Condition: Anxiety Disorders Age Group: adult Sources: |
Other AEs: Respiratory depression... Other AEs: Respiratory depression (serious|grade 5) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Abuse | serious|grade 5 | 0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Sources: |
Respiratory depression | serious|grade 5 | 0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Sources: |
Asthenia | 1 patient Disc. AE |
0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years n = 573 Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Population Size: 573 Sources: |
Hyperkinesia | 1 patient Disc. AE |
0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years n = 573 Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Population Size: 573 Sources: |
Incoordination | 1 patient Disc. AE |
0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years n = 573 Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Population Size: 573 Sources: |
Urticaria | 1 patient Disc. AE |
0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years n = 573 Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Population Size: 573 Sources: |
Vasodilatation | 1 patient Disc. AE |
0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years n = 573 Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Population Size: 573 Sources: |
Hypoventilation | 2 patients Disc. AE |
0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years n = 573 Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Population Size: 573 Sources: |
Rash | 2 patients Disc. AE |
0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years n = 573 Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Population Size: 573 Sources: |
Somnolence | 3 patients Disc. AE |
0.2 mg/kg 2 times / day multiple, rectal Recommended Dose: 0.2 mg/kg, 2 times / day Route: rectal Route: multiple Dose: 0.2 mg/kg, 2 times / day Sources: |
unhealthy, > 12 years n = 573 Health Status: unhealthy Condition: seizure activity Age Group: > 12 years Population Size: 573 Sources: |
Respiratory depression | serious|grade 5 | 10 mg 2 times / day multiple, intranasal Recommended Dose: 10 mg, 2 times / day Route: intranasal Route: multiple Dose: 10 mg, 2 times / day Co-administed with:: benzodiazepines Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Abuse | serious|grade 5 | 10 mg 4 times / day multiple, intramuscular Recommended Dose: 10 mg, 4 times / day Route: intramuscular Route: multiple Dose: 10 mg, 4 times / day Co-administed with:: benzodiazepines Sources: |
unhealthy, adult Health Status: unhealthy Condition: anxiety disorders Age Group: adult Sources: |
Respiratory depression | serious|grade 5 | 10 mg 4 times / day multiple, intramuscular Recommended Dose: 10 mg, 4 times / day Route: intramuscular Route: multiple Dose: 10 mg, 4 times / day Co-administed with:: benzodiazepines Sources: |
unhealthy, adult Health Status: unhealthy Condition: anxiety disorders Age Group: adult Sources: |
Respiratory depression | serious|grade 5 | 10 mg 4 times / day multiple, oral Recommended Dose: 10 mg, 4 times / day Route: oral Route: multiple Dose: 10 mg, 4 times / day Co-administed with:: OPIOIDS Sources: |
unhealthy, adult Health Status: unhealthy Condition: Anxiety Disorders Age Group: adult Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/020648_S002_DIASTAT_AP.pdf#page=8 Page: 8.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/020648_S002_DIASTAT_AP.pdf#page=8 Page: 8.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/020648_S002_DIASTAT_AP.pdf#page=8 Page: 8.0 |
no | |||
Page: 1.0 |
strong [IC50 2 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/8948091/ Page: 1.0 |
major | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/020648_S002_DIASTAT_AP.pdf#page=8 Page: 8.0 |
major | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/020648_S002_DIASTAT_AP.pdf#page=8 Page: 8.0 |
major | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/8948091/ Page: 1.0 |
major | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/8948091/ Page: 1.0 |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/8948091/ Page: 1.0 |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/8948091/ Page: 1.0 |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/8948091/ Page: 1.0 |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/8948091/ Page: 1.0 |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/8948091/ Page: 1.0 |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
The influence of aldosterone and anticonvulsant drugs on electroencephalographic and clinical disturbances induced by the spirolactone derivative, potassium canrenoate. | 1975 Jan |
|
Duration of amnesia during sedation with diazepam and pentazocine: preliminary report. | 1975 Jan |
|
Reactions to intravenous injections of diazepam. | 1976 Dec |
|
[Provocation of tonic seizures during intravenous faustan administration]. | 1978 Nov |
|
Chlorambucil-induced seizure in a patient with nephrotic syndrome. | 1999 |
|
Binding, partial agonism, and potentiation of alpha(1)-adrenergic receptor function by benzodiazepines: A potential site of allosteric modulation. | 1999 Dec |
|
Distinct features of seizures induced by cocaine and amphetamine analogs. | 1999 Jul 21 |
|
A fugue-like state associated with diazepam use. | 1999 Jun |
|
Severe vasculitis after therapy with diazepam. | 1999 Jun |
|
Effects of diazepam on extracellular brain neurotransmitters in pilocarpine-induced seizures in rats. | 1999 Jun 4 |
|
Anticonvulsants for soman-induced seizure activity. | 1999 Mar-Apr |
|
Transient syncope and ECG changes associated with the concurrent administration of clozapine and diazepam. | 1999 Sep |
|
Heterogeneity of GABA(A) receptor-mediated responses in the human IMR-32 neuroblastoma cell line. | 2000 May 15 |
|
Etomidate-induced convulsion prior to electroconvulsive therapy. | 2000 Oct |
|
Extracellular serotonin is enhanced in the striatum, but not in the dorsal hippocampus or prefrontal cortex, in rats subjected to an operant conflict procedure. | 2001 Feb |
|
Lack of reinforcing effect of the benzodiazepine and tricyclic antidepressant combination of diazepam and dothiepin. | 2001 Feb |
|
Diazepam in the treatment of GHB dependence. | 2001 Feb |
|
[Febrile convulsions, Treatment and prognosis]. | 2001 Feb 19 |
|
[Premedication for endoscopy]. | 2001 Feb 2 |
|
Effects of a novel uncompetitive NMDA receptor antagonist, MRZ 2/579 on ethanol self-administration and ethanol withdrawal seizures in the rat. | 2001 Feb 9 |
|
Evaluation of native GABA(A) receptors containing an alpha 5 subunit. | 2001 Feb 9 |
|
[Effect of diazepam on apnea attacks in a 6-year-old girl with Rett syndrome: a polysomnographic study]. | 2001 Jan |
|
Diazepam and nicotine increase social interaction in gerbils: a test for anxiolytic action. | 2001 Jan 12 |
|
Long-term reduction of benzodiazepine receptor density in the rat cerebellum by acute seizures and kindling and its recovery 6 months later by a pentylenetetrazole challenge. | 2001 Jan 12 |
|
Simple and sensitive high-performance liquid chromatographic method for the determination of 1,5-benzodiazepine clobazam and its active metabolite N-desmethylclobazam in human serum and urine with application to 1,4-benzodiazepines analysis. | 2001 Jan 5 |
|
Effect of leaf essential oil from Piper solmsianum C.DC. in mice behaviour. | 2001 Mar |
|
Molecular targets for the myorelaxant action of diazepam. | 2001 Mar |
|
Modulation of GABA(A) receptors by benzodiazepines and barbiturates is autonomous of PKC activation. | 2001 Mar |
|
A behavioral economic analysis of polydrug abuse in alcoholics: asymmetrical substitution of alcohol and cocaine. | 2001 Mar 1 |
|
The octadecaneuropeptide [diazepam-binding inhibitor (33-50)] exerts potent anorexigenic effects in rodents. | 2001 Mar 2 |
Name | Type | Language | ||
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Common Name | English | ||
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Systematic Name | English |
Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C1012
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DTXSID80200460
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DBSALT002258
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SUB32951
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6452650
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100000125956
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52468-36-7
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C98133
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6JD21U639H
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257-935-4
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ACTIVE MOIETY
SUBSTANCE RECORD