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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
Structure of TOFISOPAM

SMILES

CCC1C2=C(C=C(OC)C(OC)=C2)C(=NN=C1C)C3=CC(OC)=C(OC)C=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

HIDE SMILES / InChI

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 ( + / - )

Description
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.

Originator

Sources: HU155572

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.9 µM [IC50]
0.68 µM [IC50]
5.9 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Grandaxin

Approved Use

Unknown
Primary
Grandaxin

Approved Use

Unknown
Primary
Grandaxin

Approved Use

Unknown
Primary
Grandaxin

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
[Highlights of CNS research at IDR: 2,3-benzodiazepines].
2001
Tofisopam--evaluation of mutagenic and genotoxic properties.
2001 Jan-Feb
Highlights of CNS research at IDR: 2,3-benzodiazepines.
2001 Oct
Species-dependency in chiral-drug recognition of serum albumin studied by chromatographic methods.
2002 Dec 31
Immunomodulating effects of tofizopam (Grandaxin) and diazepam in vitro.
2002 Feb
Analysis of tofisopam in human serum by column-switching semi-micro high-performance liquid chromatography and evaluation of tofisopam bioequivalency.
2002 Jun
A population-based case-control teratologic study of nitrazepam, medazepam, tofisopam, alprazolum and clonazepam treatment during pregnancy.
2002 Mar 10
[A case in which tofisopam was effective for treatment of paroxysmal supraventricular tachycardia].
2003 May
[Use of grandaxine in the treatment of patients with erosive-ulcerative stomach and gastroduodenal lesions].
2004
[Peculiarities in the effect of tofisopam and valerian extract on short-term memory and anxiety states in healthy humans].
2004 Nov-Dec
[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
[Chronobiological peculiarities of tofisopam action on human heart rate variability].
2005 Jul-Aug
[Fluctuations of the antianxiety effect of valerian and grandaxin during daytime wakefulness in humans with different chronotypes].
2005 Mar-Apr
[The effect of tofisopam and tinctura leonuri on the color-discrimination function in young humans].
2005 May-Jun
Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs.
2005 Sep
[Climacteric disorders].
2006 Apr
Effect of tofisopam on the single-oral-dose pharmacokinetics and pharmacodynamics of the cyp3a4 probe drug alprazolam.
2006 Jul
Gas chromatography nitrogen phosphorous detection (GC-NPD) assay of tofisopam in human plasma for pharmacokinetic evaluation.
2006 Jun 16
[Tofisopam and melatonin attenuate the reorganization of circadian locomotor rhythm in rats under injection-induced stress conditions].
2006 Mar-Apr
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 Sep 29
Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling.
2007 May 15
In vitro prediction and in vivo verification of enantioselective human tofisopam metabolite profiles.
2007 Oct
Application of drug repositioning strategy to TOFISOPAM.
2008
Tofisopam inhibits the pharmacokinetics of CYP3A4 substrate midazolam.
2008 Jan
Clinical trial: dextofisopam in the treatment of patients with diarrhoea-predominant or alternating irritable bowel syndrome.
2008 Jan 15
[Grandaxin in neurological practice].
2009
Tenoten in the therapy of anxious disturbances in patients with essential hypertension and coronary heart disease.
2009 Aug
Benzodiazepine prescription and length of hospital stay at a Japanese university hospital.
2009 Oct 9
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis.
2010 Nov
Emerging pharmacologic therapies for irritable bowel syndrome.
2010 Oct
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Recommended dosage is 50-100mg 1-3 times a day. The maximum daily dose is 300mg.
Route of Administration: Oral
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 Sat Dec 16 15:54:31 GMT 2023
Edited
by admin
on Sat Dec 16 15:54:31 GMT 2023
Record UNII
UZC80HAU42
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TOFISOPAM
INN   MART.   MI   WHO-DD  
INN  
Official Name English
EMANDAXIN
Brand Name English
Tofisopam [WHO-DD]
Common Name English
TOFISOPAM [MI]
Common Name English
tofisopam [INN]
Common Name English
1-(3,4-DIMETHOXYPHENYL)-5-ETHYL-7,8-DIMETHOXY-4-METHYL-5H-2,3-BENZODIAZEPINE
Systematic Name English
TOFISOPAM [MART.]
Common Name English
TOFISOPAM [JAN]
Common Name English
(±)-1-(3,4-DIMETHOXYPHENYL)-5-ETHYL-7,8-DIMETHOXY-4-METHYL-5H-2,3-BENZODIAZEPINE
Systematic Name English
Classification Tree Code System Code
WHO-ATC N05BA23
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
WHO-VATC QN05BA23
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
NCI_THESAURUS C28197
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
Code System Code Type Description
EVMPD
SUB11144MIG
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
MESH
C012582
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
ECHA (EC/EINECS)
244-922-3
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
MERCK INDEX
m10932
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY Merck Index
WIKIPEDIA
TOFISOPAM
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
ChEMBL
CHEMBL404216
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
CAS
22345-47-7
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
SMS_ID
100000077749
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
DRUG BANK
DB08811
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
RXCUI
38365
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY RxNorm
FDA UNII
UZC80HAU42
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
DRUG CENTRAL
2693
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
EPA CompTox
DTXSID3023681
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
INN
3130
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
NCI_THESAURUS
C90791
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
PUBCHEM
5502
Created by admin on Sat Dec 16 15:54:31 GMT 2023 , Edited by admin on Sat Dec 16 15:54:31 GMT 2023
PRIMARY
Related Record Type Details
ENANTIOMER -> RACEMATE
ENANTIOMER -> RACEMATE
Related Record Type Details
ACTIVE MOIETY