Identification
- Summary
Temazepam is a short-acting benzodiazepine commonly used to treat panic disorders, severe anxiety, and insomnia.
- Brand Names
- Restoril
- Generic Name
- Temazepam
- DrugBank Accession Number
- DB00231
- Background
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
Structure for Temazepam (DB00231)
- 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.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to manage Insomnia Combination Product in combination with: Choline (DB00122) •••••••••••• Management of Insomnia •••••••••••• - Contraindications & Blackbox Warnings
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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.
Target Actions Organism AGABA(A) Receptor positive allosteric modulatorHumans UGABA(A) Receptor Benzodiazepine Binding Site ligandHumans - 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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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Temazepam is combined with 1,2-Benzodiazepine. Abacavir Temazepam may decrease the excretion rate of Abacavir which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Temazepam which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Temazepam which could result in a higher serum level. Acetaminophen Temazepam may decrease the excretion rate of Acetaminophen which could result in a higher serum level. - Food Interactions
- Avoid alcohol.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Temazepam hydrochloride IA4EP07006 97598-16-8 GPVUAFAZVYNKRQ-UHFFFAOYSA-N Temazepam sulfate I1HX8463I0 31677-86-8 XNBFXTXDZMWXMN-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Euhypnos / Norkotral / Normison / Nortem / Remestan / Temaze / Temtabs
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Co Temazepam Capsules 15mg Capsule 15 mg Oral Cobalt Laboratories 2002-08-14 2015-08-07 Canada 
Co Temazepam Capsules 30mg Capsule 30 mg Oral Cobalt Laboratories 2002-08-14 2015-08-07 Canada Restoril Capsule 30 mg/1 Oral Physicians Total Care, Inc. 2003-10-31 2011-05-31 US 
Restoril Capsule 7.5 mg/1 Oral SpecGx LLC 1981-02-27 Not applicable US Restoril Capsule 15 mg Oral Aa Pharma Inc 1980-12-31 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-temazepam Capsule 30 mg Oral Apotex Corporation 1996-10-02 Not applicable Canada Apo-temazepam Capsule 15 mg Oral Apotex Corporation 1996-10-02 Not applicable Canada Dom-temazepam Capsule 30 mg Oral Dominion Pharmacal 1997-03-16 2016-10-25 Canada Dom-temazepam Capsule 15 mg Oral Dominion Pharmacal 1996-12-16 2016-10-25 Canada Gen-temazepam 15mg Capsule 15 mg Oral Genpharm Ulc 1997-07-08 2009-10-15 Canada - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Strazepam Temazepam (15 mg/1) + Choline (250 mg/1) Kit Oral Physician Therapeutics Llc 2011-02-15 Not applicable US
Categories
- ATC Codes
- N05CD07 — Temazepam
- Drug Categories
- Anti-Anxiety Agents
- Benzazepines
- Benzodiazepine hypnotics and sedatives
- Benzodiazepines and benzodiazepine derivatives
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- GABA Agents
- GABA Modulators
- Heterocyclic Compounds, Fused-Ring
- Hypnotics and Sedatives
- Muscle Relaxants
- Muscle Relaxants, Centrally Acting Agents
- Psychotropic Drugs
- Tranquilizing Agents
- 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)
- Affected organisms
- Humans and other mammals
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
- 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. [Article]
- Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines]. Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. [Article]
- Vozeh S: [Pharmacokinetic of benzodiazepines in old age]. Schweiz Med Wochenschr. 1981 Nov 21;111(47):1789-93. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Ochs HR, Greenblatt DJ, Verburg-Ochs B, Matlis R: Temazepam clearance unaltered in cirrhosis. Am J Gastroenterol. 1986 Jan;81(1):80-4. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Electronic Medicines Compendium: Temazepam 10mg Tablets Monograph [Link]
- Temazepam Capsules USP 15 mg and 30 mg Canadian Product Monograph [File]
- Temazepam Fact Sheet from http://cdn.neiglobal.com/content/pg/live/temazepam.pdf [File]
- External Links
- Human Metabolome Database
- HMDB0014376
- KEGG Drug
- D00370
- KEGG Compound
- C07125
- PubChem Compound
- 5391
- PubChem Substance
- 46506604
- ChemSpider
- 5198
- BindingDB
- 50408032
- 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
- FDA label
- Download (260 KB)
- MSDS
- Download (530 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Human Immunodeficiency Virus (HIV) Infections / Insomnia 1 4 Completed Treatment Insomnia 1 3 Completed Treatment Chronic Obstructive Pulmonary Disease (COPD) 1 3 Terminated Treatment Anxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia 1 1 Completed Treatment Insomnia 1
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
Form Route Strength Capsule Oral Solution / drops Suppository Capsule Oral 15 mg / cap Capsule Oral 30 mg / cap Capsule Oral 30 mg Capsule Oral 20 MG Capsule Oral 10 MG Kit Oral Capsule Oral 15 mg/1 Capsule Oral 15 mg Capsule Oral 22.5 mg/1 Capsule Oral 30 mg/1 Capsule Oral 7.5 mg/1 - Prices
Unit description Cost Unit Restoril 22.5 mg capsule 11.37USD capsule Restoril 7.5 mg capsule 11.37USD capsule Temazepam 22.5 mg capsule 9.94USD capsule Temazepam 7.5 mg capsule 9.94USD capsule Restoril 15 mg capsule 7.87USD capsule Restoril 30 mg capsule 7.67USD capsule Temazepam 30 mg capsule 0.69USD capsule Temazepam 15 mg capsule 0.58USD capsule Apo-Temazepam 30 mg Capsule 0.14USD capsule Co Temazepam 30 mg Capsule 0.14USD capsule Novo-Temazepam 30 mg Capsule 0.14USD capsule Pms-Temazepam 30 mg Capsule 0.14USD capsule Ratio-Temazepam 30 mg Capsule 0.14USD capsule Apo-Temazepam 15 mg Capsule 0.12USD capsule Co Temazepam 15 mg Capsule 0.12USD capsule Novo-Temazepam 15 mg Capsule 0.12USD capsule Pms-Temazepam 15 mg Capsule 0.12USD capsule Ratio-Temazepam 15 mg Capsule 0.12USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5211954 No 1993-05-18 2010-05-18 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 119-121 °C PhysProp water solubility 164 mg/L Not Available logP 2.19 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.0534 mg/mL ALOGPS logP 2.16 ALOGPS logP 2.79 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 10.68 Chemaxon pKa (Strongest Basic) -1.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 52.9 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 81.01 m3·mol-1 Chemaxon Polarizability 30.32 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9913 Blood Brain Barrier + 0.9745 Caco-2 permeable + 0.7979 P-glycoprotein substrate Non-substrate 0.55 P-glycoprotein inhibitor I Non-inhibitor 0.7388 P-glycoprotein inhibitor II Inhibitor 0.546 Renal organic cation transporter Non-inhibitor 0.7776 CYP450 2C9 substrate Non-substrate 0.6281 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.6962 CYP450 1A2 substrate Inhibitor 0.5916 CYP450 2C9 inhibitor Non-inhibitor 0.5454 CYP450 2D6 inhibitor Non-inhibitor 0.891 CYP450 2C19 inhibitor Non-inhibitor 0.5615 CYP450 3A4 inhibitor Non-inhibitor 0.6014 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6494 Ames test Non AMES toxic 0.7974 Carcinogenicity Non-carcinogens 0.8093 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.0888 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9987 hERG inhibition (predictor II) Non-inhibitor 0.8308
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 171.0607803 predictedDarkChem Lite v0.1.0 [M-H]- 166.2145 predictedDeepCCS 1.0 (2019) [M+H]+ 171.0943803 predictedDarkChem Lite v0.1.0 [M+H]+ 168.5725 predictedDeepCCS 1.0 (2019) [M+Na]+ 170.7590803 predictedDarkChem Lite v0.1.0 [M+Na]+ 174.66563 predictedDeepCCS 1.0 (2019)
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
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
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
- 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. [Article]
- 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
- 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. [Article]
- 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
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55