Camazepam

Identification

Name
Camazepam
Accession Number
DB01489
Type
Small Molecule
Groups
Experimental, Illicit
Description

Camazepam is a benzodiazepine which is a dimethyl carbamate ester of tamzepam, a metabolite of diazepam. Similarly to other drugs in its class, it has antxiolytic, anticonvulsant, hypnotic, and skeletal muscle relaxant properties. However, unlike other benzodiapeines camazepam is predominantly anxiolytic and is relatively weak as an anticonvulsant, hypnotic and skeletal muscle relaxant.

Camazepam also has less side effects, such as impaired cognition and reaction times, compared to other benzodiazepines. However, impairment of cognition and disrupted sleep patterns will occur at doses higher than 40mg of carazepam. Camazepam is also believed to increase attention, and is associated with skin disorders.

In the United States camazepam is regulated as a Schedule IV controlled substance.

Structure
Thumb
Synonyms
Not Available
International/Other Brands
Albego (Boehringer Ingelheim) / Limpidon (Crinos) / Paxor
Categories
UNII
HZ3XRH03C3
CAS number
36104-80-0
Weight
Average: 371.818
Monoisotopic: 371.103669164
Chemical Formula
C19H18ClN3O3
InChI Key
PXBVEXGRHZFEOF-UHFFFAOYSA-N
InChI
InChI=1S/C19H18ClN3O3/c1-22(2)19(25)26-17-18(24)23(3)15-10-9-13(20)11-14(15)16(21-17)12-7-5-4-6-8-12/h4-11,17H,1-3H3
IUPAC Name
7-chloro-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl N,N-dimethylcarbamate
SMILES
CN(C)C(=O)OC1N=C(C2=CC=CC=C2)C2=C(C=CC(Cl)=C2)N(C)C1=O

Pharmacology

Indication

Camazepam has been used in placebo controlled studies for the treatment of patients suffering from anxiety and depression.

Pharmacodynamics
Not Available
Mechanism of action

Camazepam has been shown to bind competitively to benzodiazepine receptors in the brain with a relatively low affinity in animal models. This binding of benzodiazepine receptors by camazepam and its active metabolites is responsible for its anticonvulsant effects. Notably, only three metabolites were shown to exert anticonvulsant activity, temazepam, oxazepam, and hydroxy camazepam.

The anxiolytic properties of camazepam are also attributed to their ability to bind benzodiazepine receptors, also known as GABA receptors. When benzodiazepines bind to GABA receptors they increase the efficiency with which the inhibitory neurotransmitter GABA binds.

Absorption

Almost completely absorbed into the bloodstream after oral administration. 90% bioavailability can be achieved in humans.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolized by the liver into more than 10 metabolites, some of which are also active and posses anticonvulsant properties. [3] One active metabolite of note is temazepam which has roughly equal in effectiveness as an anxiolytic, but is less anticonvulsant, sedating, and motor-impairing.

Camazepam undergoes enantioselective metabolism by human liver microsomes. [1]

Route of elimination

Renally eliminated.

Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Camazepam is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe therapeutic efficacy of Camazepam can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Camazepam is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Camazepam.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Camazepam.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Camazepam is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe therapeutic efficacy of Camazepam can be decreased when used in combination with 6-O-benzylguanine.
7-DeazaguanineThe therapeutic efficacy of Camazepam can be decreased when used in combination with 7-Deazaguanine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Camazepam is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Camazepam is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
Food Interactions
Not Available

References

Synthesis Reference

Ferrari, G. and Casagrande, C.; U.S. Patent 3,799,920; March 26,1974; assigned to Siphar SA.

General References
  1. Lu XL, Yang SK: Enantiomer resolution of camazepam and its derivatives and enantioselective metabolism of camazepam by human liver microsomes. J Chromatogr A. 1994 Apr 22;666(1-2):249-57. [PubMed:7911374]
  2. Morino A, Sasaki H, Mukai H, Sugiyama M: Receptor-mediated model relating anticonvulsant effect to brain levels of camazepam in the presence of its active metabolites. J Pharmacokinet Biopharm. 1986 Jun;14(3):309-21. [PubMed:2878071]
  3. Morino A, Sugiyama M: Relation between time courses of pharmacological effects and of plasma levels of camazepam and its active metabolites in rats. J Pharmacobiodyn. 1985 Aug;8(8):597-606. [PubMed:2868088]
External Links
KEGG Drug
D07315
PubChem Compound
37367
PubChem Substance
46505921
ChemSpider
34285
ChEBI
135570
ChEMBL
CHEMBL1095282
Wikipedia
Camazepam
ATC Codes
N05BA15 — Camazepam

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)173-174Ferrari, G. and Casagrande, C.; U.S. Patent 3,799,920; March 26,1974; assigned to Siphar SA.
Predicted Properties
PropertyValueSource
Water Solubility0.0182 mg/mLALOGPS
logP2.48ALOGPS
logP3.34ChemAxon
logS-4.3ALOGPS
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area62.21 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity98.63 m3·mol-1ChemAxon
Polarizability38.05 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9966
Blood Brain Barrier+0.9578
Caco-2 permeable+0.5746
P-glycoprotein substrateSubstrate0.5311
P-glycoprotein inhibitor IInhibitor0.7291
P-glycoprotein inhibitor IIInhibitor0.7616
Renal organic cation transporterNon-inhibitor0.881
CYP450 2C9 substrateNon-substrate0.6792
CYP450 2D6 substrateNon-substrate0.8325
CYP450 3A4 substrateSubstrate0.7293
CYP450 1A2 substrateNon-inhibitor0.7304
CYP450 2C9 inhibitorNon-inhibitor0.6194
CYP450 2D6 inhibitorNon-inhibitor0.8758
CYP450 2C19 inhibitorInhibitor0.5491
CYP450 3A4 inhibitorNon-inhibitor0.7769
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6962
Ames testNon AMES toxic0.6493
CarcinogenicityNon-carcinogens0.7149
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9995 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9973
hERG inhibition (predictor II)Non-inhibitor0.6456
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
Mass Spectrum (Electron Ionization)MSsplash10-00di-9260000000-edfba1a5fcbe9ca50d1d
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 / Benzene and substituted derivatives / Aryl chlorides / Tertiary carboxylic acid amides / Carbamate esters / Organic carbonic acids and derivatives / Lactams / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds
show 5 more
Substituents
1,4-benzodiazepine / Alpha-amino acid or derivatives / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Carbamic acid ester / Tertiary carboxylic acid amide / Carboxamide group / Ketimine
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Drug created on July 31, 2007 07:09 / Updated on November 02, 2018 05:02