Identification

Name
Lormetazepam
Accession Number
DB13872
Type
Small Molecule
Groups
Approved
Description

Lormatazepam is an orally available benzodiazepine used in the UK for the treatment of short-term insomnia 2. It is marketed by Auden Mckenzie (Pharma Division) in 0.5 and 1 mg tablet formulations.

Structure
Thumb
Synonyms
  • (±)-Lormetazepam
  • (RS)-Lormetazepam
  • 7-Chloro-1,3-dihydro-5-(o-chlorophenyl)-3-hydroxy-1-methyl-2H-1,4-benzodiazepin-2-one
  • 7-Chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-1-methyl-2H-1,4-benzodiazepin-2-one
  • Methyllorazepam
  • N-Methyllorazepam
Categories
UNII
GU56C842ZA
CAS number
848-75-9
Weight
Average: 335.185
Monoisotopic: 334.027583052
Chemical Formula
C16H12Cl2N2O2
InChI Key
FJIKWRGCXUCUIG-UHFFFAOYSA-N
InChI
InChI=1S/C16H12Cl2N2O2/c1-20-13-7-6-9(17)8-11(13)14(19-15(21)16(20)22)10-4-2-3-5-12(10)18/h2-8,15,21H,1H3
IUPAC Name
7-chloro-5-(2-chlorophenyl)-3-hydroxy-1-methyl-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=C1Cl

Pharmacology

Indication

For the treatment of short-term insomnia 2

Pharmacodynamics

Lormetazepam is a benzodiazepine which reduces central nervous system (CNS) activity 2,1. It produces anxiolytic, muscle relaxant, sedative and hypnotic effects. Because it is a short-acting benzodiapine, it does not produce significant sedation after waking.

Mechanism of action

Lormetazepam, as a benzodiazepine, binds to the regulatory site between the α and γ subunits of γ-aminobutryic acid (GABA) A receptors with γ2 and α1, α2, α3, or α5 subunits 1. This facilitates the opening of the chloride channel allowing chloride ions to flow into the neuron resulting in hyperpolarization. Hyperpolarized neurons require greater simulation to reach their action potential threshold. The general inhibitory effect on neuronal depolarization produces the effects of lormetazepam.

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
AGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolised to an inactive metabolite via glucuronide conjugation 2

Route of elimination
Not Available
Half life

The terminal phase half life is 11 h 2.

Clearance
Not Available
Toxicity

The primary manifestation of overdosage ranges from drowsiness to coma and symptoms may include ataxia, hypotension, hypotonia, respiratory depression which may lead to death 2.

Experimental LD50 values are as follows 3: Mouse - 780 mg/kg (intraperitoneal), 1790 mg/kg (oral), 10000 mg/kg (subcutaneous). Rat - 6250 mg/kg (intraperitoneal), 10000 mg/kg (oral), 10000 mg/kg (intraperitoneal).

Affected organisms
Not Available
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
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Lormetazepam is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe therapeutic efficacy of Lormetazepam can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Lormetazepam.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Lormetazepam.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Lormetazepam is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe therapeutic efficacy of Lormetazepam can be decreased when used in combination with 6-O-benzylguanine.
7-DeazaguanineThe therapeutic efficacy of Lormetazepam can be decreased when used in combination with 7-Deazaguanine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Lormetazepam.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Lormetazepam.
7,9-DimethylguanineThe therapeutic efficacy of Lormetazepam can be decreased when used in combination with 7,9-Dimethylguanine.
Additional Data Available
  • Extended Description
    Extended Description

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

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. 43. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 533-534). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  2. MRHA: Lormetazepam Summary of Product Characteristics [Link]
  3. ChemIDPlus: Lormetazepam [Link]
External Links
Human Metabolome Database
HMDB0041919
PubChem Compound
13314
PubChem Substance
347829324
ChemSpider
12750
RxNav
28894
ChEBI
52993
ChEMBL
CHEMBL22097
Wikipedia
Lormetazepam
ATC Codes
N05CD06 — Lormetazepam
MSDS
Download (49.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentSleep Initiation and Maintenance Disorders1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenia1
3TerminatedTreatmentSleep Initiation and Maintenance Disorders1
4Active Not RecruitingTreatmentSedation in Intensive Care Unit Patients1
Not AvailableCompletedNot AvailableIllness, Critical1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0164 mg/mLALOGPS
logP2.92ALOGPS
logP3.39ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)10.68ChemAxon
pKa (Strongest Basic)-2.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.9 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity85.82 m3·mol-1ChemAxon
Polarizability32.21 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0a4i-1219000000-503deaa645713d28cd79
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-2739000000-db8dc59f3b0cd2b1f961
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

Taxonomy

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 / Chlorobenzenes / 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 / Alpha-amino acid or derivatives / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Tertiary carboxylic acid amide / Carboxamide group
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, 1,4-benzodiazepinone (CHEBI:52993)

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
Yes
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. 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]

Drug created on July 07, 2017 15:36 / Updated on June 12, 2020 11:42

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