General
Preferred name
DIAZEPAM
Synonyms
PMID27607364-Compound-4 ()
Dialar Fte ()
Diastat Acudial ()
Relanium ()
Nrl-1 ()
Diastat ()
Ansiolisina ()
Paxel ()
RO 5-2807 ()
Alupram 10 ()
E-Pam ()
Valrelease ()
Valium ()
Apozepam ()
Alupram 5 ()
Atensine ()
Diazepam Intensol ()
Alupram 2 ()
RO-5-2807 ()
Dialar ()
LA-III ()
NSC-77518 ()
Tensium ()
WY-3467 ()
Scriptopam ()
Valclair ()
Servizepam ()
Serenack ()
Solis ()
Ro-52807 ()
Valtoco ()
NSC-169897 ()
Centrazepam ()
Tranimul ()
Diacepin ()
Dizac ()
Q-Pam ()
LA III ()
Diazepam civ ()
Vivol ()
Tranquase ()
Stesolid ()
Diazepam-d8 ()
Diazepam-d5 (CRM) ()
Diazepam-d8 (exempt preparation) ()
P&D ID
PD003026
CAS
11100-37-1
439-14-5
83056-50-2
65854-76-4
1536200-31-3
Tags
natural product
drug
available
Approved by
FDA
First approval
1963
Drug Status
illicit
investigational
approved
vet_approved
Drug indication
Epilepsy
Sedative-Hypnotic
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Diazepam is a benzodiazepine that exerts anxiolytic, sedative, muscle- relaxant, anticonvulsant and amnestic effects [F3157, F3160, L5188]. Most of these effects are thought to result from facilitation of the action of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system [F3157, F3160, L5188].
ROE
Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates [F3157, F3160, L5188].
INDICATION
In general, diazepam is useful in the symptomatic management of mild to moderate degrees of anxiety in conditions dominated by tension, excitation, agitation, fear, or aggressiveness such as may occur in psychoneurosis, anxiety reactions due to stress conditions, and anxiety states with somatic expression [F3160]. Moreover, in acute alcoholic withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor, and impending acute delirium tremens [F3160]. Furthermore, diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathologies, such as inflammation of the muscle and joints or secondary to trauma; spasticity caused by upper motor neuron disorders, such as cerebral palsy and paraplegia; athetosis and the rare "stiff man syndrome" [F3160]. Particular label information from the United Kingdom also lists particular age-specific indications, including for adults: (1) The short-term relief (2-4 weeks) only, of anxiety which is severe, disabling, or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic or psychotic illness, (2) cerebral palsy, (3) muscle spasm, (4) as an adjunct to certain types of epilepsy (eg. myoclonus), (5) symptomatic treatment of acute alcohol withdrawal, (6) as oral premedication for the nervous dental patient, and (7) for premedication before surgery [L5188]. In the same UK label information, diazepam is indicated in children for: (1) control of tension and irritability in cerebral spasticity in selected cases, (2) as an adjunct to the control of muscle spasm in tetanus, and for (3) oral premedication [L5188].
METABOLISM
Diazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam [F3157, F3160]. N-desmethyldiazepam and temazepam are both further metabolized to oxazepam [F3157, F3160]. Temazepam and oxazepam are further largely eliminated by way of conjugation to glucuronic acid via glucuronidation [F3157, F3160]. Furthermore, oxidation of diazepam is mediated by cytochrome P450 isozymes; formation of desmethyl-diazepam mainly by CYP2C19 and CYP3A and 3-hydroxy-diazepam (temazepam) and oxazepam by CYP3A. Because CYP2C19 is polymorphic, extensive metabolizers (EMs), and poor metabolizers (PMs) of diazepam can be distinguished [F3157, F3160]. PMs of diazepam showed significantly lower clearance (12 vs 26 mL/min) and longer elimination half-life (88 vs 41 h) of diazepam than EMs after a single oral dose [F3157, F3160]. Also, PMs had lower clearance, higher AUC and longer elimination half-life of desmethyl-diazepam [F3157, F3160].
HALF-LIFE
Diazepam has a biphasic half-life with an initial rapid distribution phase followed by a prolonged terminal elimination phase of 1 or 2 days; its action is further prolonged by the even longer half-life of 2-5 days of its principal active metabolite, desmethyldiazepam (nordiazepam), the relative proportion of which increases in the body on long-term administration [L5188]. The plasma half-life of diazepam is prolonged in neonates, in the elderly, and in patients with kidney or liver disease [L5188].
MOA
Diazepam is a benzodiazepine tranquilliser with anticonvulsant, sedative, muscle relaxant and amnesic properties [F3157, F3160, L5188].; ; Benzodiazepines, such as diazepam, bind to receptors in various regions of the brain and spinal cord. This binding increases the inhibitory effects of gamma-aminobutyric acid (GABA) [F3157, F3160, L5188]. GABAs functions include CNS involvement in sleep induction. Also involved in the control of hypnosis, memory, anxiety, epilepsy and neuronal excitability [F3157, F3160, L5188].
ABSORPTION
After oral administration, it is considered that diazepam is rapidly and completely absorbed from the gastrointestinal tract as >90% of diazepam is absorbed and the average time to achieve peak plasma concentrations is 1 â 1.5 hours with a range of 0.25 to 2.5 hours [F3157, F3160, L5188].; ; Absorption is delayed and decreased when administered with a moderate fat meal [F3157]. In the presence of food mean lag times are approximately 45 minutes as compared with 15 minutes when fasting [F3157]. There is also an increase in the average time to achieve peak concentrations to about 2.5 hours in the presence of food as compared with 1.25 hours when fasting [F3157]. This results in an average decrease in Cmax of 20% in addition to a 27% decrease in AUC (range 15% to 50%) when administered with food [F3157].
DESCRIPTION
Diazepam is a benzodiazepine drug with long acting anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties.
(GtoPdb)
MOA
Diazepam is a benzodiazepine tranquilliser with anticonvulsant, sedative, muscle relaxant and amnesic properties [F3157, F3160, L5188]. Benzodiazepines, such as diazepam, bind to receptors in various regions of the brain and spinal cord. This binding increases the inhibitory effects of gamma-aminobutyric acid (GABA) [F3157, F3160, L5188]. GABAs functions include CNS involvement in sleep induction. Also involved in the control of hypnosis, memory, anxiety, epilepsy and neuronal excitability [F3157, F3160, L5188].
ABSORPTION
After oral administration, it is considered that diazepam is rapidly and completely absorbed from the gastrointestinal tract as >90% of diazepam is absorbed and the average time to achieve peak plasma concentrations is 1 â 1.5 hours with a range of 0.25 to 2.5 hours [F3157, F3160, L5188]. Absorption is delayed and decreased when administered with a moderate fat meal [F3157]. In the presence of food mean lag times are approximately 45 minutes as compared with 15 minutes when fasting [F3157]. There is also an increase in the average time to achieve peak concentrations to about 2.5 hours in the presence of food as compared with 1.25 hours when fasting [F3157]. This results in an average decrease in Cmax of 20% in addition to a 27% decrease in AUC (range 15% to 50%) when administered with food [F3157].
INDICATION
In general, diazepam is useful in the symptomatic management of mild to moderate degrees of anxiety in conditions dominated by tension, excitation, agitation, fear, or aggressiveness such as may occur in psychoneurosis, anxiety reactions due to stress conditions, and anxiety states with somatic expression [F3160].; ; Moreover, in acute alcoholic withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor, and impending acute delirium tremens [F3160].; ; Furthermore, diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathologies, such as inflammation of the muscle and joints or secondary to trauma; spasticity caused by upper motor neuron disorders, such as cerebral palsy and paraplegia; athetosis and the rare "stiff man syndrome" [F3160].; ; Particular label information from the United Kingdom also lists particular age-specific indications, including for adults: (1) The short-term relief (2-4 weeks) only, of anxiety which is severe, disabling, or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic or psychotic illness, (2) cerebral palsy, (3) muscle spasm, (4) as an adjunct to certain types of epilepsy (eg. myoclonus), (5) symptomatic treatment of acute alcohol withdrawal, (6) as oral premedication for the nervous dental patient, and (7) for premedication before surgery [L5188].; ; In the same UK label information, diazepam is indicated in children for: (1) control of tension and irritability in cerebral spasticity in selected cases, (2) as an adjunct to the control of muscle spasm in tetanus, and for (3) oral premedication [L5188].
METABOLISM
Diazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam [F3157, F3160]. N-desmethyldiazepam and temazepam are both further metabolized to oxazepam [F3157, F3160]. Temazepam and oxazepam are further largely eliminated by way of conjugation to glucuronic acid via glucuronidation [F3157, F3160].; ; Furthermore, oxidation of diazepam is mediated by cytochrome P450 isozymes; formation of desmethyl-diazepam mainly by CYP2C19 and CYP3A and 3-hydroxy-diazepam (temazepam) and oxazepam by CYP3A. Because CYP2C19 is polymorphic, extensive metabolizers (EMs), and poor metabolizers (PMs) of diazepam can be distinguished [F3157, F3160]. PMs of diazepam showed significantly lower clearance (12 vs 26 mL/min) and longer elimination half-life (88 vs 41 h) of diazepam than EMs after a single oral dose [F3157, F3160]. Also, PMs had lower clearance, higher AUC and longer elimination half-life of desmethyl-diazepam [F3157, F3160].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
1
Organisms
0
Compound Sets
24
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP Approved Drugs
DrugMatrix
Guide to Pharmacology
IPPI - DB
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
ReFrame library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
70
Properties
(calculated by RDKit )
Molecular Weight
284.07
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
0
Rotatable Bonds
1
Ring Count
3
Aromatic Ring Count
2
cLogP
3.15
TPSA
32.67
Fraction CSP3
0.12
Chiral centers
0.0
Largest ring
7.0
QED
0.79
Structural alerts
0
No structural alerts detected
Custom attributes
(extracted from source data)
Member status
virtual
MOA
GABA(A) BZ Site Receptor Agonists
Source data