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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2020-02-26 21:42:04 UTC
HMDB IDHMDB0015699
Secondary Accession Numbers
  • HMDB15699
Metabolite Identification
Common NameTofisopam
DescriptionTofisopam, also known as emandaxin or egyt-341, belongs to the class of organic compounds known as benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms). Peak plasma levels are attained two hours after an oral dose. While it may not be an anticonvulsant in and of itself, it has been shown to enhance the anticonvulsant action of classical 1,4-benzodiazepines (such as diazepam) and muscimol, but not sodium valproate, carbamazepine, phenobarbital, or phenytoin. Tofisopam is not reported as causing dependence to the same extent as other benzodiazepines, but is still recommended to be prescribed for a maximum of 12 weeks. Tofisopam is a drug. Tofisopam is an extremely weak basic (essentially neutral) compound (based on its pKa). Tofisopam is a potentially toxic compound. Tofisopam is also claimed to be a PDE10A inhibitor, which may provide an alternative mechanism of action for its various therapeutic effects, and this action has been proposed to make tofisopam potentially useful as a treatment for schizophrenia. Tofisopam is indicated for the treatment of anxiety and alcohol withdrawal, and is prescribed in a dosage of 50–300 mg per day divided into three doses. However, Vela Pharmaceuticals of New Jersey is developing the D-enantiomer (dextofisopam) as a treatment for irritable bowel syndrome, with moderate efficacy demonstrated in clinical trials so far. Chemically, it is a 2,3-benzodiazepine. Tofisopam (Emandaxin, Grandaxin, Sériel) is an anxiolytic that is marketed in several European countries.
Structure
Data?1582753324
Synonyms
ValueSource
EmandaxinKegg
TofizopamHMDB
EGYT-341HMDB
LevotofisopamHMDB
DextofisopamHMDB
GrandaxinHMDB
1-(3,4-Dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepineHMDB
Chemical FormulaC22H26N2O4
Average Molecular Weight382.4528
Monoisotopic Molecular Weight382.18925733
IUPAC Name1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine
Traditional Nameseriel
CAS Registry Number22345-47-7
SMILES
CCC1C2=CC(OC)=C(OC)C=C2C(=NN=C1C)C1=CC(OC)=C(OC)C=C1
InChI Identifier
InChI=1S/C22H26N2O4/c1-7-15-13(2)23-24-22(14-8-9-18(25-3)19(10-14)26-4)17-12-21(28-6)20(27-5)11-16(15)17/h8-12,15H,7H2,1-6H3
InChI KeyRUJBDQSFYCKFAA-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodiazepines
Sub ClassNot Available
Direct ParentBenzodiazepines
Alternative Parents
Substituents
  • Benzodiazepine
  • Dimethoxybenzene
  • O-dimethoxybenzene
  • Phenoxy compound
  • Anisole
  • Phenol ether
  • Methoxybenzene
  • Alkyl aryl ether
  • Monocyclic benzene moiety
  • Benzenoid
  • Ether
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Physiological effect

Health effect:

Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point152 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0024 g/LALOGPS
logP4.29ALOGPS
logP3.83ChemAxon
logS-5.2ALOGPS
pKa (Strongest Basic)-2.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area61.64 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity109.03 m³·mol⁻¹ChemAxon
Polarizability42.14 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-014i-0039000000-5cb577edbbc8cc8d6873Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0009000000-37ba280ae280f0151420Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-9138000000-45b5e7b9478d1c0dcc70Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-06vi-3935000000-4b7b313aca10282cc22aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0009000000-6678f5bee5aedc2c1c6cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00lr-0009000000-c7930084c12118c44738Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000j-0059000000-dc272a4e40d2fd95dfa8Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB08811 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB08811 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB08811
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID5301
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTofisopam
METLIN IDNot Available
PubChem Compound5502
PDB IDNot Available
ChEBI ID518452
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Rundfeldt C, Socala K, Wlaz P: The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. doi: 10.1007/s00702-010-0507-3. Epub 2010 Oct 22. [PubMed:20967473 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (By similarity).
Gene Name:
PDE3A
Uniprot ID:
Q14432
Molecular weight:
124978.06
References
  1. Rundfeldt C, Socala K, Wlaz P: The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. doi: 10.1007/s00702-010-0507-3. Epub 2010 Oct 22. [PubMed:20967473 ]
General function:
Involved in catalytic activity
Specific function:
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.
Gene Name:
PDE10A
Uniprot ID:
Q9Y233
Molecular weight:
89388.7
References
  1. Rundfeldt C, Socala K, Wlaz P: The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. doi: 10.1007/s00702-010-0507-3. Epub 2010 Oct 22. [PubMed:20967473 ]
General function:
Involved in catalytic activity
Specific function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
Gene Name:
PDE2A
Uniprot ID:
O00408
Molecular weight:
105145.485
References
  1. Rundfeldt C, Socala K, Wlaz P: The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. doi: 10.1007/s00702-010-0507-3. Epub 2010 Oct 22. [PubMed:20967473 ]
General function:
Involved in 3',5'-cyclic-nucleotide phosphodiesterase activity
Specific function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4A
Uniprot ID:
P27815
Molecular weight:
98142.155
References
  1. Rundfeldt C, Socala K, Wlaz P: The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. doi: 10.1007/s00702-010-0507-3. Epub 2010 Oct 22. [PubMed:20967473 ]
General function:
Involved in monooxygenase 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Toth M, Bajnogel J, Egyed A, Drabant S, Tomlo J, Klebovich I: [Effect of tofisopam on CYP3A4 enzyme activity on human recombinant 3A4 supersome]. Acta Pharm Hung. 2005;75(4):195-8. [PubMed:16711396 ]