U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description

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

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Grandaxin
Primary
Grandaxin
Primary
Grandaxin
Primary
Grandaxin

Doses

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

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
In Vitro Use Guide
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
Record UNII
UZC80HAU42
Record Status Validated (UNII)
Record Version