Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C22H26N2O4 |
| Molecular Weight | 382.4528 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCC1C2=CC(OC)=C(OC)C=C2C(=NN=C1C)C3=CC=C(OC)C(OC)=C3
InChI
InChIKey=RUJBDQSFYCKFAA-UHFFFAOYSA-N
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
| Molecular Formula | C22H26N2O4 |
| Molecular Weight | 382.4528 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
DescriptionSources: https://www.drugbank.ca/drugs/DB08811Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21920746 | https://www.ncbi.nlm.nih.gov/pubmed/18027916 | https://topbrainboosters.com/grandaxin/ | https://www.ncbi.nlm.nih.gov/pubmed/10670703
Sources: https://www.drugbank.ca/drugs/DB08811
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21920746 | https://www.ncbi.nlm.nih.gov/pubmed/18027916 | https://topbrainboosters.com/grandaxin/ | https://www.ncbi.nlm.nih.gov/pubmed/10670703
Tofisopam (marketed under brand names Emandaxin and Grandaxin) is a 2,3-benzodiazepine derivative that is marketed in several European countries as the anxiolytic drug. Tofisopam does not bind to the benzodiazepine binding site of the gamma-aminobutyric acid receptor. One study has shown that tofisopam acts as an isoenzyme-selective inhibitor of phosphodiesterases (PDEs) with the highest affinity to PDE-4A1 followed by PDE-10A1, PDE-3, and PDE-2A3. Like other benzodiazepines, tofisopam possesses anxiolytic properties but unlike other benzodiazepines, it does not have anticonvulsant, sedative, skeletal muscle relaxant, motor skill-impairing or amnestic properties. 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 (but not sodium valproate, carbamazepine, phenobarbital, or phenytoin). Tofisopam is not approved for sale in the United States or Canada. 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.
CNS Activity
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2760 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18027916 |
|||
Target ID: CHEMBL2169736 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21920746 |
0.9 µM [IC50] | ||
Target ID: CHEMBL2093863 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21920746 |
0.68 µM [IC50] | ||
Target ID: CHEMBL2094125 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21920746 |
5.9 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Grandaxin Approved UseUnknown |
|||
Sources: https://topbrainboosters.com/grandaxin/ |
Primary | Grandaxin Approved UseUnknown |
||
| Primary | Grandaxin Approved UseUnknown |
|||
| Primary | Grandaxin Approved UseUnknown |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| yes [IC50 0.8 uM] | yes (co-administration study) Comment: Tofisopam increased Midazolam AUCinf by 140% and Cmax by 94%. Sources: https://pubmed.ncbi.nlm.nih.gov/17989974/ |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | ||||
| major | ||||
| minor | ||||
| minor | ||||
| minor | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method. | 2010-12 |
|
| The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. | 2010-11 |
|
| Emerging pharmacologic therapies for irritable bowel syndrome. | 2010-10 |
|
| Benzodiazepine prescription and length of hospital stay at a Japanese university hospital. | 2009-10-09 |
|
| Tenoten in the therapy of anxious disturbances in patients with essential hypertension and coronary heart disease. | 2009-08 |
|
| [Grandaxin in neurological practice]. | 2009 |
|
| Clinical trial: dextofisopam in the treatment of patients with diarrhoea-predominant or alternating irritable bowel syndrome. | 2008-01-15 |
|
| Tofisopam inhibits the pharmacokinetics of CYP3A4 substrate midazolam. | 2008-01 |
|
| Application of drug repositioning strategy to TOFISOPAM. | 2008 |
|
| In vitro prediction and in vivo verification of enantioselective human tofisopam metabolite profiles. | 2007-10 |
|
| Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling. | 2007-05-15 |
|
| Method validation and determination of enantiomers and conformers in tofisopam drug substances and drug products by chiral high-performance liquid chromatography and kinetic and thermodynamic study of the interconversion of the conformers. | 2006-09-29 |
|
| [Tofisopam and melatonin attenuate the reorganization of circadian locomotor rhythm in rats under injection-induced stress conditions]. | 2006-07-19 |
|
| Effect of tofisopam on the single-oral-dose pharmacokinetics and pharmacodynamics of the cyp3a4 probe drug alprazolam. | 2006-07 |
|
| Gas chromatography nitrogen phosphorous detection (GC-NPD) assay of tofisopam in human plasma for pharmacokinetic evaluation. | 2006-06-16 |
|
| [Climacteric disorders]. | 2006-04 |
|
| [Chronobiological peculiarities of tofisopam action on human heart rate variability]. | 2005-10-01 |
|
| Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs. | 2005-09 |
|
| [The effect of tofisopam and tinctura leonuri on the color-discrimination function in young humans]. | 2005-07-29 |
|
| [Fluctuations of the antianxiety effect of valerian and grandaxin during daytime wakefulness in humans with different chronotypes]. | 2005-05-14 |
|
| [Peculiarities in the effect of tofisopam and valerian extract on short-term memory and anxiety states in healthy humans]. | 2005-02-15 |
|
| [Use of grandaxin in hypermotor dysfunction of the biliary ducts in young people]. | 2005 |
|
| [Effect of tofisopam on CYP3A4 enzyme activity on human recombinant 3A4 supersome]. | 2005 |
|
| Risk and benefit of drug use during pregnancy. | 2005 |
|
| [Use of grandaxine in the treatment of patients with erosive-ulcerative stomach and gastroduodenal lesions]. | 2004 |
|
| [A case in which tofisopam was effective for treatment of paroxysmal supraventricular tachycardia]. | 2003-05 |
|
| Species-dependency in chiral-drug recognition of serum albumin studied by chromatographic methods. | 2002-12-31 |
|
| Analysis of tofisopam in human serum by column-switching semi-micro high-performance liquid chromatography and evaluation of tofisopam bioequivalency. | 2002-06 |
|
| A population-based case-control teratologic study of nitrazepam, medazepam, tofisopam, alprazolum and clonazepam treatment during pregnancy. | 2002-03-10 |
|
| Immunomodulating effects of tofizopam (Grandaxin) and diazepam in vitro. | 2002-02 |
|
| Highlights of CNS research at IDR: 2,3-benzodiazepines. | 2001-10 |
|
| Tofisopam--evaluation of mutagenic and genotoxic properties. | 2001-05-24 |
|
| [Highlights of CNS research at IDR: 2,3-benzodiazepines]. | 2001 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://topbrainboosters.com/grandaxin/
Recommended dosage is 50-100mg 1-3 times a day. The maximum daily dose is 300mg.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17646282
All microsomal incubations were conducted in 100 mM phosphate buffer, pH 7.4, initiated by the addition of NADPH (1 mM final concentration), and stopped by the addition of 0.5 ml of ethyl acetate and vortexing after a predetermined incubation time period. Pilot microsomal incubations were conducted to determine appropriate concentrations of tofisopam and human liver microsomal protein, as well as incubation time. On the basis of these pilot incubations, the following incubation conditions were used for the remainder of the microsomal work: 500 ng/ml tofisopam, 0.2 mg/ml human liver microsomes, and a 10-min incubation time.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Apr 02 06:54:09 GMT 2025
by
admin
on
Wed Apr 02 06:54:09 GMT 2025
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| Record UNII |
UZC80HAU42
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| Record Status |
Validated (UNII)
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WHO-ATC |
N05BA23
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WHO-VATC |
QN05BA23
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NCI_THESAURUS |
C28197
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SUB11144MIG
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C012582
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244-922-3
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m10932
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TOFISOPAM
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CHEMBL404216
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22345-47-7
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100000077749
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DB08811
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38365
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UZC80HAU42
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2693
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DTXSID3023681
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3130
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C90791
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5502
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ENANTIOMER -> RACEMATE | |||
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ENANTIOMER -> RACEMATE |
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ACTIVE MOIETY |