Identification

Name
Temazepam
Accession Number
DB00231
Description

Temazepam, like many other similar and related benzodiazepines, acts as a gamma-aminobutyric acid (GABA) modulator and is capable of eliciting a variety of actions including sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action 6,7,13,14.

Although the chemical synthesis of temazepam was established by 1965 9, mainstream contemporary use of the medication did not occur until it's legitimate use as treatment for insomnia was accepted and approved later on. In particular, before temazepam saw regular prescription use in civilians it was - and still is - employed by the US military as a sedative-hypnotic medication to be taken by soldiers, pilots, etc. to obtain the necessary rest required for medical recovery or scheduled maneuvers and operations 10. Regardless, temazepam has become one of the most frequently prescribed medications internationally and sees millions of prescriptions every year. Unfortunately, however, given its frequent use and the inherent nature of its pharmacological effects, temazepam - like many other benzodiazepines - possesses a high potential for misuse and is genuinely capable of developing drug tolerance, physical dependence, and addiction in users.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 300.74
Monoisotopic: 300.066555377
Chemical Formula
C16H13ClN2O2
Synonyms
  • Temazepam
External IDs
  • WY-3917

Pharmacology

Indication

Temazepam is specifically indicated only for the short-term management of insomnia Label, 12. Furthermore, such management is generally predominantly associated with the symptomatic relief of transient and short-term insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings and/or early morning awakenings 13. In particular, the official prescribing information for temazepam typically specifies that the instructions issued for dispensed prescriptions of the medication should indicate specifically that patients are only expected to use the therapy for short periods of time - usually 7-10 days in general Label,13. Subsequently, treatment with temazepam should usually not exceed 7 to 10 consecutive days and nor should it be prescribed in quantities exceeding a one-month supply 13.

Some regional prescribing information also notes that temazepam may be used for premedication prior to minor surgery or other related procedures 12.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Temazepam is a benzodiazepine used as a hypnotic agent in the management of insomnia Label 6,7,12,13,14. Temazepam produces CNS depression at limbic, thalamic, and hypothalamic levels of the CNS 6,7,13,14. Temazepam increases the affinity of the neurotransmitter gamma-aminobutyric acid (GABA) for GABA receptors by binding to benzodiazepine receptors 6,7,13,14. Results are sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action 6,7,13,14.

In sleep laboratory studies, the effect of temazepam was compared to placebo during a two week period 13. The studies demonstrated a linear dose-response improvement in total sleep time and sleep latency with substantial drug-placebo differences apparent for total sleep time and for sleep latency at higher doses of temazepam 13. Regardless, REM sleep was ultimately unchanged but slow wave sleep was decreased 13.

Moreover, a transient syndrome, known as "rebound insomnia", wherein the symptoms that led to treatment with temazepam in the first place recur in an enhanced form, may happen on withdrawal of temazepam treatment 13. The possibility of this occurrence is in part why long term use of temazepam is not recommended due to worries over tolerance and dependence wherein patients' bodies become physiologically accustomed to the regular presence and pharmacological effect of higher and higher doses of the benzodiazepine used 13.

The duration of hypnotic effect and the profile of unwanted adverse effects may be influenced by the distribution and elimination half-lives of the administered temazepam and any active metabolites that may be formed 13. When such half-lives are long, the drug or its metabolite(s) may accumulate during periods of nightly administration and be associated with impairments of cognitive and motor performance during waking hours 13. Conversely, if half-lives are short, the drug and metabolites would be cleared before the next dose is ingested, and carry-over effects related to sedation or CNS depression should be minimal or not present at all 13. However, during nightly use and for an extended period, pharmacodynamic tolerance or adaptation to some effects of benzodiazepine hypnotics may develop - which may also contribute to the possibility of 'rebound insomnia' 13.

Consequently, if the drug has a very short elimination half-life, it is possible that a relative deficiency (for example, in relation to benzodiazepine GABA(a) receptor sites) may occur at some point in the interval between each night's use 13. This sequence of events may account for certain clinical findings reported happening after several weeks of nightly use of rapidly eliminated benzodiazepine hypnotics, including increased wakefulness during the last third of the night and the appearance of increased daytime anxiety 13.

Mechanism of action

Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body 6,7,13,14. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors 6,7,13,14. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons 6,7,13,14.

Subsequently, benzodiazepines like temazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors 6,7,13,14. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors 6,7,13,14. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells 6,7,13,14. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action 6,7,13,14.

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
UGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
Absorption

Studies demonstrate that between 90 to 100% of an orally administered temazepam dose is absorbed, making the medication very well absorbed 13,12. The oral administration of 15 to 45 mg temazepam resulted in rapid absorption with significant blood levels achieved in 30 minutes and peak levels at 2-3 hours 13,12. In particular, direct studies following the oral ingestion of 30 mg of temazepam revealed measurable plasma concentrations were obtained 10-20 minutes after dosing with peak plasma levels ranging between 666-982 ng/mL (with a mean of 865 ng/mL) presenting approximately 1.2-1.6 hours (with a mean of 1.5 hours) after the dosing Label. Finally, a dose-proportional relationship was established for the area under the plasma concentration/time curve over the 15 to 30 mg dose range Label.

Volume of distribution

The volume of distribution documented for temazepam is 1.3-1.5 L/kg body weight - and in particular, 43-68 L/kg for the unbound fraction 12.

Protein binding

It has been recorded that about 96% of unchanged temazepam is bound to plasma proteins 13,12.

Metabolism

First-pass metabolism of temazepam is minimal at approximately 5-8% of an administered dose 13,12. Nevertheless, temazepam is principally metabolized in the liver where most of the unchanged drug is directly conjugated to glucuronide and excreted in the urine 13,12. In particular, the primary metabolite present in the blood is the O-conjugate of temazepam Label,13,12. Less than 5% of the drug is demethylated to oxazepam and subsequently eliminated as the glucuronide 13,12. Regardless, the glucuronides of temazepam have no demonstrable CNS activity and it is believed that no active metabolites are formed in general Label,13,12. Since temazepam mainly undergoes Phase II conjugation reactions, it is proposed that it is devoid of CYP450 interactions.11

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Route of elimination

Following a single dose, 80-90% of the dose appears in the urine, predominantly as the O-conjugate metabolite, and 3-13% of the dose appears in the faeces Label 13,12. Less than 2% of the dose is excreted unchanged or as N-desmethyltemazepam in the urine Label 13,12.

Half-life

The terminal half-life determined for temazepam is recorded as being between 3.5-18 hours, with a mean of 9 hours 13,12.

Clearance

Studies regarding the clearance of temazepam have recorded the values of 1.03 ml/min/kg and 31 ml/min/kg for the clearance of total temazepam and the clearance of unbound temazepam, respectively 8.

Adverse Effects
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Toxicity

Manifestations of acute overdosage of temazepam, as with other benzodiazepines, can be expected to reflect the increasing CNS effects of the drug and include somnolence, confusion, and coma, with reduced or absent reflexes Label 12,13,14. With large overdoses, respiratory depression, hypotension, and finally coma can occur Label 12,13,14.

Benzodiazepines like temazepam might cause fetal harm when administered to a pregnant woman. Transplacental distribution has in the past resulted in neonatal CNS depression following the ingestion of therapeutic doses of related benzodiazepine hypnotics like diazepam during the last weeks of pregnancy Label 12,13,14.

It is not known whether this drug is excreted in human milk Label 12,13,14. Caution should, therefore, be exercised when temazepam is administered to a nursing woman Label 12,13,14.

Safety and effectiveness in pediatric patients have not been established Label 12,13,14.

Lower doses of temazepam, like 7.5 mg is recommended as the initial dosage for patients aged 65 and over since the risk of the development of oversedation, dizziness, confusion, ataxia and/or falls increases substantially with larger doses of benzodiazepines in elderly and debilitated patients Label 12,13,14.

No evidence of carcinogenicity was observed in animal studies although hyperplastic liver nodules were observed in female mice exposed to the highest doses of temazepam Label 12,13,14. The clinical significance of this finding is not known Label 12,13,14.

Fertility in male and female rats was not adversely affected by temazepam toxicity studies Label 12,13,14.

No mutagenicity tests have been done with temazepam Label 12,13,14.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirTemazepam may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseTemazepam may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Temazepam which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Temazepam which could result in a higher serum level.
AcetaminophenTemazepam may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideThe risk or severity of adverse effects can be increased when Temazepam is combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Temazepam is combined with Acetophenazine.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Temazepam which could result in a higher serum level.
AclidiniumTemazepam may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AcrivastineTemazepam may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
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Food Interactions
  • Avoid alcohol.
  • Take with or without food.

Products

Product Ingredients
IngredientUNIICASInChI Key
Temazepam hydrochlorideIA4EP0700697598-16-8GPVUAFAZVYNKRQ-UHFFFAOYSA-N
Temazepam sulfateI1HX8463I031677-86-8XNBFXTXDZMWXMN-UHFFFAOYSA-N
Product Images
International/Other Brands
Euhypnos / Norkotral / Normison / Nortem / Remestan / Temaze / Temtabs
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Co Temazepam Capsules 15mgCapsuleOralCobalt Laboratories2002-08-142015-08-07Canada flag
Co Temazepam Capsules 30mgCapsuleOralCobalt Laboratories2002-08-142015-08-07Canada flag
RestorilCapsule30 mg/1OralPhysicians Total Care, Inc.2003-10-312011-05-31US flag
RestorilCapsule30 mg/1OralSpecGx LLC1981-02-27Not applicableUS flag
RestorilCapsule30 mgOralAa Pharma Inc1980-12-31Not applicableCanada flag
RestorilCapsule7.5 mg/1OralSpecGx LLC1981-02-27Not applicableUS flag
RestorilCapsule15 mg/1OralPhysicians Total Care, Inc.2002-01-252012-06-30US flag
RestorilCapsule22.5 mg/1OralSpecGx LLC1981-02-27Not applicableUS flag
RestorilCapsule15 mgOralAa Pharma Inc1980-12-31Not applicableCanada flag
RestorilCapsule7.5 mg/1OralPhysicians Total Care, Inc.2007-01-082012-06-30US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Dom-temazepamCapsuleOralDominion Pharmacal1996-12-162016-10-25Canada flag
Dom-temazepamCapsuleOralDominion Pharmacal1997-03-162016-10-25Canada flag
Gen-temazepam 15mgCapsuleOralGenpharm Ulc1997-07-082009-10-15Canada flag
Gen-temazepam 30mgCapsuleOralGenpharm Ulc1997-07-082009-10-15Canada flag
Ntp-temazepamCapsuleOralNt Pharma Canada LtdNot applicableNot applicableCanada flag
Ntp-temazepamCapsuleOralNt Pharma Canada LtdNot applicableNot applicableCanada flag
Nu-temazepamCapsuleOralNu Pharm Inc1996-08-162012-09-04Canada flag
Nu-temazepamCapsuleOralNu Pharm Inc1996-08-162012-09-04Canada flag
Penta-temazepam CapsulesCapsuleOralPentapharm Ltd.Not applicableNot applicableCanada flag
Penta-temazepam CapsulesCapsuleOralPentapharm Ltd.Not applicableNot applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
StrazepamTemazepam (15 mg/1) + Choline (250 mg/1)KitOralPhysician Therapeutics Llc2011-02-15Not applicableUS flag

Categories

ATC Codes
N05CD07 — Temazepam
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
1,4-benzodiazepines
Direct Parent
1,4-benzodiazepines
Alternative Parents
Alpha amino acids and derivatives / Benzene and substituted derivatives / Aryl chlorides / Tertiary carboxylic acid amides / Lactams / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Alkanolamines / Organopnictogen compounds
show 4 more
Substituents
1,4-benzodiazepine / Alkanolamine / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxamide group
show 17 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzodiazepine (CHEBI:9435)

Chemical Identifiers

UNII
CHB1QD2QSS
CAS number
846-50-4
InChI Key
SEQDDYPDSLOBDC-UHFFFAOYSA-N
InChI
InChI=1S/C16H13ClN2O2/c1-19-13-8-7-11(17)9-12(13)14(18-15(20)16(19)21)10-5-3-2-4-6-10/h2-9,15,20H,1H3
IUPAC Name
7-chloro-3-hydroxy-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one
SMILES
CN1C2=C(C=C(Cl)C=C2)C(=NC(O)C1=O)C1=CC=CC=C1

References

General References
  1. 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:2883820]
  2. Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines]. Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. [PubMed:2570451]
  3. Vozeh S: [Pharmacokinetic of benzodiazepines in old age]. Schweiz Med Wochenschr. 1981 Nov 21;111(47):1789-93. [PubMed:6118950]
  4. Shats V, Kozacov S: [Falls in the geriatric department: responsibility of the care-giver and the hospital]. Harefuah. 1995 Jun 1;128(11):690-3, 743. [PubMed:7557666]
  5. Rooke KC: The use of flurazepam (dalmane) as a substitute for barbiturates and methaqualone/diphenhydramine (mandrax) in general practice. J Int Med Res. 1976;4(5):355-9. [PubMed:18375]
  6. Heel RC, Brogden RN, Speight TM, Avery GS: Temazepam: a review of its pharmacological properties and therapeutic efficacy as an hypnotic. Drugs. 1981 May;21(5):321-40. doi: 10.2165/00003495-198121050-00001. [PubMed:6112127]
  7. Fraschini F, Stankov B: Temazepam: pharmacological profile of a benzodiazepine and new trends in its clinical application. Pharmacol Res. 1993 Feb-Mar;27(2):97-113. doi: 10.1006/phrs.1993.1011. [PubMed:8474963]
  8. Ochs HR, Greenblatt DJ, Verburg-Ochs B, Matlis R: Temazepam clearance unaltered in cirrhosis. Am J Gastroenterol. 1986 Jan;81(1):80-4. [PubMed:2867675]
  9. Maggini C, Murri M, Sacchetti G: Evaluation of the effectiveness of temazepam on the insomnia of patients with neurosis and endogenous depression. Arzneimittelforschung. 1969 Oct;19(10):1647-52. [PubMed:4311716]
  10. Caldwell JA, Caldwell JL: Fatigue in military aviation: an overview of US military-approved pharmacological countermeasures. Aviat Space Environ Med. 2005 Jul;76(7 Suppl):C39-51. [PubMed:16018329]
  11. English BA, Dortch M, Ereshefsky L, Jhee S: Clinically significant psychotropic drug-drug interactions in the primary care setting. Curr Psychiatry Rep. 2012 Aug;14(4):376-90. doi: 10.1007/s11920-012-0284-9. [PubMed:22707017]
  12. Electronic Medicines Compendium: Temazepam 10mg Tablets Monograph [Link]
  13. Temazepam Capsules USP 15 mg and 30 mg Canadian Product Monograph [File]
  14. Temazepam Fact Sheet from http://cdn.neiglobal.com/content/pg/live/temazepam.pdf [File]
Human Metabolome Database
HMDB0014376
KEGG Drug
D00370
KEGG Compound
C07125
PubChem Compound
5391
PubChem Substance
46506604
ChemSpider
5198
BindingDB
50408032
RxNav
10355
ChEBI
9435
ChEMBL
CHEMBL967
Therapeutic Targets Database
DAP000238
PharmGKB
PA451608
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Temazepam
AHFS Codes
  • 28:24.08 — Benzodiazepines
FDA label
Download (260 KB)
MSDS
Download (530 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Insomnia1
4CompletedTreatmentInsomnia1
3CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenia1
1CompletedTreatmentInsomnia1
Not AvailableCompletedTreatmentHigh-altitude Sleep Disturbance1

Pharmacoeconomics

Manufacturers
  • Tyco healthcare group lp
  • Quantum pharmics ltd
  • Actavis elizabeth llc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Novel laboratories inc
  • Sandoz inc
  • Usl pharma inc
  • Watson laboratories inc
Packagers
  • Actavis Group
  • Aidarex Pharmacuticals LLC
  • Amerisource Health Services Corp.
  • A-S Medication Solutions LLC
  • Ascend Laboratories LLC
  • Bryant Ranch Prepack
  • Cardinal Health
  • Caremark LLC
  • Corepharma LLC
  • D.M. Graham Laboratories Inc.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Novartis AG
  • Novel Laboratories Inc.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Sunbreaker Usa
  • UDL Laboratories
  • Va Cmop Dallas
Dosage Forms
FormRouteStrength
CapsuleOral
CapsuleOral20 MG
CapsuleOral10 MG
CapsuleOral15 mg
CapsuleOral30 mg
KitOral
CapsuleOral15 mg/1
CapsuleOral22.5 mg/1
CapsuleOral30 mg/1
CapsuleOral7.5 mg/1
Prices
Unit descriptionCostUnit
Restoril 22.5 mg capsule11.37USD capsule
Restoril 7.5 mg capsule11.37USD capsule
Temazepam 22.5 mg capsule9.94USD capsule
Temazepam 7.5 mg capsule9.94USD capsule
Restoril 15 mg capsule7.87USD capsule
Restoril 30 mg capsule7.67USD capsule
Temazepam 30 mg capsule0.69USD capsule
Temazepam 15 mg capsule0.58USD capsule
Apo-Temazepam 30 mg Capsule0.14USD capsule
Co Temazepam 30 mg Capsule0.14USD capsule
Novo-Temazepam 30 mg Capsule0.14USD capsule
Pms-Temazepam 30 mg Capsule0.14USD capsule
Ratio-Temazepam 30 mg Capsule0.14USD capsule
Apo-Temazepam 15 mg Capsule0.12USD capsule
Co Temazepam 15 mg Capsule0.12USD capsule
Novo-Temazepam 15 mg Capsule0.12USD capsule
Pms-Temazepam 15 mg Capsule0.12USD capsule
Ratio-Temazepam 15 mg Capsule0.12USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5211954No1993-05-182010-05-18US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)119-121 °CPhysProp
water solubility164 mg/LNot Available
logP2.19HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0534 mg/mLALOGPS
logP2.16ALOGPS
logP2.79ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)10.68ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.9 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity81.01 m3·mol-1ChemAxon
Polarizability30.32 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9913
Blood Brain Barrier+0.9745
Caco-2 permeable+0.7979
P-glycoprotein substrateNon-substrate0.55
P-glycoprotein inhibitor INon-inhibitor0.7388
P-glycoprotein inhibitor IIInhibitor0.546
Renal organic cation transporterNon-inhibitor0.7776
CYP450 2C9 substrateNon-substrate0.6281
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6962
CYP450 1A2 substrateInhibitor0.5916
CYP450 2C9 inhibitorNon-inhibitor0.5454
CYP450 2D6 inhibitorNon-inhibitor0.891
CYP450 2C19 inhibitorNon-inhibitor0.5615
CYP450 3A4 inhibitorNon-inhibitor0.6014
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6494
Ames testNon AMES toxic0.7974
CarcinogenicityNon-carcinogens0.8093
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.0888 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9987
hERG inhibition (predictor II)Non-inhibitor0.8308
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-00di-4391000000-eba55d0cdbd09c877424
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0019000000-f9c9fe92391b593143eb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0091000000-b26b004678460e39d9db
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0090000000-d71ab75b6d551af5cf29
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0390000000-43e671827e9519f8cbd7
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a6r-0980000000-6fcab627ec42157d1ed9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0092000000-36017deb260bb70b05cd

Targets

Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [PubMed:23038269]
  2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [PubMed:29950725]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
Curator comments
Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [PubMed:29950725]
  2. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [PubMed:23038269]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Shou M, Mei Q, Ettore MW Jr, Dai R, Baillie TA, Rushmore TH: Sigmoidal kinetic model for two co-operative substrate-binding sites in a cytochrome P450 3A4 active site: an example of the metabolism of diazepam and its derivatives. Biochem J. 1999 Jun 15;340 ( Pt 3):845-53. [PubMed:10359672]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Ono S, Hatanaka T, Miyazawa S, Tsutsui M, Aoyama T, Gonzalez FJ, Satoh T: Human liver microsomal diazepam metabolism using cDNA-expressed cytochrome P450s: role of CYP2B6, 2C19 and the 3A subfamily. Xenobiotica. 1996 Nov;26(11):1155-66. doi: 10.3109/00498259609050260. [PubMed:8948091]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2020 01:55

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