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Details

Stereochemistry ACHIRAL
Molecular Formula C16H13ClN2O.ClH
Molecular Weight 321.2016
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIAZEPAM HYDROCHLORIDE

SMILES

CN1c2ccc(cc2C(=NCC1=O)c3ccccc3)Cl.Cl

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

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C16H13ClN2O
Molecular Weight 284.7408
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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.

Originator

Curator's Comment:: # Hoffmann-La Roche

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
8.6 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VALIUM

Approved Use

Valium 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 Date

-1.93449607E11
Palliative
VALIUM

Approved Use

Valium 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 Date

-1.93449607E11
Palliative
VALIUM

Approved Use

Valium 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 Date

-1.93449607E11
Palliative
VALIUM

Approved Use

Valium 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 Date

-1.93449607E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
317 ng/mL
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
1530 ng × h/mL
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
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
48 h
unknown, oral
DIAZEPAM plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
unknown, oral
DIAZEPAM plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2000 mg single, oral
Overdose
Dose: 2000 mg
Route: oral
Route: single
Dose: 2000 mg
Sources:
healthy, 28 years
Health Status: healthy
Age Group: 28 years
Sex: M
Sources:
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Sources:
unhealthy, 61 years
Health Status: unhealthy
Age Group: 61 years
Sex: F
Sources:
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)
Abuse (serious|grade 5)
Sources:
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)
Hypoventilation (2 patients)
Rash (2 patients)
Asthenia (1 patient)
Hyperkinesia (1 patient)
Incoordination (1 patient)
Vasodilatation (1 patient)
Urticaria (1 patient)
Sources:
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
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)
Abuse (serious|grade 5)
Sources:
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

AEs

AESignificanceDosePopulation
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
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:
OverviewDrug as perpetrator​Drug as victimTox targets
PubMed

PubMed

TitleDatePubMed
Letter: Clonazepam in the treatment of drug-induced dyskinesia.
1975 Feb 1
[The mechanism of the anticonvulsive action of diazepam].
1975 Mar
The effect of cold and diazepam on the toxicity of fenfluramine in mice.
1975 Mar 15
Diazepam withdrawal syndrome: a case with psychosis, seizure, and coma.
1979 Jan
Influence of adenosine agonists and antiepileptic drugs on theophylline-induced seizures in rats.
1998 Oct
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
Effects of diazepam on extracellular brain neurotransmitters in pilocarpine-induced seizures in rats.
1999 Jun 4
Involvement of nitric oxide and nitric oxide synthase activity in anticonvulsive action.
1999 Mar 1
Effects of L-arginine on picrotoxin-induced increase in brain ammonia concentrations and convulsions in rats.
1999 Oct
Transient syncope and ECG changes associated with the concurrent administration of clozapine and diazepam.
1999 Sep
Syndrome of inappropriate secretion of antidiuretic hormone complicating neonatal diazepam withdrawal.
2000 Apr
Seizures caused by possible interaction between olanzapine and clomipramine.
2000 Apr
The pharmacodynamics of PK 11195 in diazepam-dependent male and female rats.
2000 Aug
Acute adverse reaction to fentanyl in a 55 year old man.
2000 Aug
Randomized, double-blind, placebo-controlled trial of diazepam, nitroglycerin, or both for treatment of patients with potential cocaine-associated acute coronary syndromes.
2000 Aug
Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats.
2000 Aug
Manic episode in an ifosfamide-treated patient.
2000 Jan-Feb
Mice lacking the long splice variant of the gamma 2 subunit of the GABA(A) receptor are more sensitive to benzodiazepines.
2000 Jun
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
Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.
2000 Oct
Flumazenil prevents diazepam-elicited anticonvulsant action and concomitant attenuation of glutamate overflow.
2000 Oct 27
Prenatal stress and postnatal development of neonatal rats--sex-dependent effects on emotional behavior and learning ability of neonatal rats.
2001 Feb
Acyl-CoA binding protein is essential in bloodstream form Trypanosoma brucei.
2001 Feb
Lack of reinforcing effect of the benzodiazepine and tricyclic antidepressant combination of diazepam and dothiepin.
2001 Feb
Regional and subunit-specific downregulation of acid-sensing ion channels in the pilocarpine model of epilepsy.
2001 Feb
Diazepam in the treatment of GHB dependence.
2001 Feb
[Febrile convulsions, Treatment and prognosis].
2001 Feb 19
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
Chronic benzodiazepine administration facilitates the subsequent development of ethanol dependence.
2001 Feb 9
Effect of diazepam and midazolam on the antinociceptive effect of morphine, metamizol and indomethacin in mice.
2001 Jan
Neuropharmacological actions of some binuclear lanthanide(III) complexes.
2001 Jan
Sedative properties of the decoction of the rhizome of Cyperus articulatus.
2001 Jan
Treatment of nonfebrile status epilepticus in Rochester, Minn, from 1965 through 1984.
2001 Jan
Effects of antiepileptic drugs on rat platelet aggregation: ex vivo and in vitro study.
2001 Jan
The efficacy of oral clonidine premedication in the prevention of postoperative vomiting in children following strabismus surgery.
2001 Jan
Enhanced cortical extracellular levels of cholecystokinin-like material in a model of anticipation of social defeat in the rat.
2001 Jan 1
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
Detection of aneuploidy in rodent and human sperm by multicolor FISH after chronic exposure to diazepam.
2001 Jan 25
Topical anesthesia for cataract surgery: a population-based perspective.
2001 Mar
Evidence for a common binding cavity for three general anesthetics within the GABAA receptor.
2001 Mar 15
Female gastrin-releasing peptide receptor (GRP-R)-deficient mice exhibit altered social preference for male conspecifics: implications for GRP/GRP-R modulation of GABAergic function.
2001 Mar 16
Systemic EMD 68843 injections reduce anxiety in the shock-probe, but not the plus-maze test.
2001 Mar 2
The octadecaneuropeptide [diazepam-binding inhibitor (33-50)] exerts potent anorexigenic effects in rodents.
2001 Mar 2
Targeted disruption of the GABA(A) receptor delta subunit gene leads to an up-regulation of gamma 2 subunit-containing receptors in cerebellar granule cells.
2001 Mar 30
The R100Q mutation of the GABA(A) alpha(6) receptor subunit may contribute to voluntary aversion to ethanol in the sNP rat line.
2001 Mar 5
Patents

Sample Use Guides

Tale 2-10 mg, 2 to 4 times daily.
Route of Administration: Oral
In Vitro Use Guide
Sources: www.ncbi.nlm.nih.gov/pubmed/6722533
Rat brain membranes were treated with diazepam (1-1000 nM) and the drug was shown to enhance the effects of iontophoretically applied GABA.
Substance Class Chemical
Created
by admin
on Sat Jun 26 15:30:17 UTC 2021
Edited
by admin
on Sat Jun 26 15:30:17 UTC 2021
Record UNII
6JD21U639H
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DIAZEPAM HYDROCHLORIDE
Common Name English
7-CHLORO-1,3-DIHYDRO-1-METHYL-5-PHENYL-2H-1,4-BENZODIAZEPIN-2-ONE HYDROCHLORIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1012
Created by admin on Sat Jun 26 15:30:17 UTC 2021 , Edited by admin on Sat Jun 26 15:30:17 UTC 2021
Code System Code Type Description
EPA CompTox
52468-36-7
Created by admin on Sat Jun 26 15:30:17 UTC 2021 , Edited by admin on Sat Jun 26 15:30:17 UTC 2021
PRIMARY
DRUG BANK
DBSALT002258
Created by admin on Sat Jun 26 15:30:17 UTC 2021 , Edited by admin on Sat Jun 26 15:30:17 UTC 2021
PRIMARY
EVMPD
SUB32951
Created by admin on Sat Jun 26 15:30:17 UTC 2021 , Edited by admin on Sat Jun 26 15:30:17 UTC 2021
PRIMARY
PUBCHEM
6452650
Created by admin on Sat Jun 26 15:30:17 UTC 2021 , Edited by admin on Sat Jun 26 15:30:17 UTC 2021
PRIMARY
CAS
52468-36-7
Created by admin on Sat Jun 26 15:30:17 UTC 2021 , Edited by admin on Sat Jun 26 15:30:17 UTC 2021
PRIMARY
NCI_THESAURUS
C98133
Created by admin on Sat Jun 26 15:30:17 UTC 2021 , Edited by admin on Sat Jun 26 15:30:17 UTC 2021
PRIMARY
FDA UNII
6JD21U639H
Created by admin on Sat Jun 26 15:30:17 UTC 2021 , Edited by admin on Sat Jun 26 15:30:17 UTC 2021
PRIMARY
ECHA (EC/EINECS)
257-935-4
Created by admin on Sat Jun 26 15:30:17 UTC 2021 , Edited by admin on Sat Jun 26 15:30:17 UTC 2021
PRIMARY
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY