Tofisopam

Last updated
Tofisopam
Tofisopam structure.svg
Tofisopam ball-and-stick model.png
Clinical data
Other names6-(3,4-Dimethoxyphenyl)-2-ethyl-9,10-dimethoxy-3-methyl-4,5-diazabicyclo[5.4.0]undeca-3,5,7,9,11-pentaene
AHFS/Drugs.com International Drug Names
Routes of
administration
By mouth (tablets)
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolism Hepatic
Elimination half-life 3 hours [1] [2]
Excretion Renal
Identifiers
  • 1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.040.823 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H26N2O4
Molar mass 382.5 g·mol−1
3D model (JSmol)
  • O(c3ccc(C\2=N\N=C(/C(c1c/2cc(OC)c(OC)c1)CC)C)cc3OC)C
  • 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 Yes check.svgY
  • Key:RUJBDQSFYCKFAA-UHFFFAOYSA-N Yes check.svgY
   (verify)

Tofisopam [3] (Emandaxin, Grandaxin, Sériel) is an anxiolytic that is marketed in several European countries. [4] Chemically, it is a 2,3-benzodiazepine. Unlike other anxiolytic benzodiazepines (which are generally 1,4- or 1,5-substituted) however, tofisopam does not have anticonvulsant, sedative, [5] skeletal muscle relaxant, motor skill-impairing or amnestic [6] 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) and muscimol, but not sodium valproate, carbamazepine, phenobarbital, or phenytoin. [7] [8] 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. Peak plasma levels are attained two hours after an oral dose. 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.

Contents

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, [9] with moderate efficacy demonstrated in clinical trials so far. [10]

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. [11]

Tofisopam has been shown to act as an inhibitor of the liver enzyme CYP3A4, [12] [13] and some researches suspect that this could cause dangerous drug interactions with other medications metabolised by this enzyme, [14] [15] although the clinical significance of these findings remains unclear.

Synthesis

Thieme Synthesis: Patent: Tofisopam synthesis.svg
Thieme Synthesis: Patent:

The halogenation of 3-(3,4-dimethoxyphenyl)pentan-2-one [105638-31-1] (1) with N-bromosuccinimide gives CID:69769657 (2). Preotection of the ketone with ethylene glycol gives CID:85840638 (3). Reaction with 3,4-dimethoxy-N,N-dimethylbenzamide [6967-45-9] (4) gives CID:11189615 (5'). Deprotection gave [15462-91-6] (6). Reaction with hydrazine completed the synthesis of tofisopam (7).

Related Research Articles

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<span class="mw-page-title-main">Clorazepate</span> Benzodiazepine medication

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<span class="mw-page-title-main">Loprazolam</span> Benzodiazepine

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<span class="mw-page-title-main">Premazepam</span> Chemical compound

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<span class="mw-page-title-main">Diclazepam</span> Chemical compound

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References

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  3. DE Patent 2122070
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