Tofisopam: Difference between revisions

{{drugbox

| Verifiedfields = changed

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = UZC80HAU42

| verifiedrevid = 408965739

|

|IUPAC_name = 1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5''H''-2,3-benzodiazepine

|synonyms = <small>6-(3,4-dimethoxyphenyl)-2-ethyl-9,10-dimethoxy-3-methyl-4,5-diazabicyclo[5.4.0]undeca-3,5,7,9,11-pentaene</small>

| image = Tofisopam.png

| image2 = Tofisopam3d.png

| width=160

| InChI = 1/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

| InChIKey = RUJBDQSFYCKFAA-UHFFFAOYAV

| smiles = O(c3ccc(C\2=N\N=C(/C(c1c/2cc(OC)c(OC)c1)CC)C)cc3OC)C

| CAS_number=22345-47-7

| ATC_prefix=N05

| ATC_suffix=BA23

| ATC_supplemental=

| PubChem=5502

| DrugBank = DB08811

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D01254

| C = 22 | H = 26 | N = 2 | O = 4

| molecular_weight = 382.5

| bioavailability= ?

| metabolism = [[Liver|Hepatic]]

| elimination_half-life= 6-8 hours

| excretion = [[Kidney|Renal]]

| pregnancy_category = ?

| legal_status = ?

| routes_of_administration= Oral

'''Tofisopam''' (marketed under brand names '''Emandaxin''' and '''Grandaxin''') is a drug which is a [[benzodiazepine]] derivative. Like other benzodiazepines, it possesses [[anxiolytic]] properties but unlike other benzodiazepines it does not have [[anticonvulsant]], [[sedative]],<ref name=definitely_not_diazepam>{{cite journal | first = A | last = Bond | coauthors = M. Lader | year = 1982 | title = A comparison of the psychotropic profiles of tofisopam and diazepam. | journal = European Journal of Clinical Pharmacology | volume = 22 | issue = 2 | pages = 137–42 | pmid = 6124424 | doi = 10.1007/BF00542458}}</ref> [[muscle relaxant|skeletal muscle relaxant]], [[motor skill]]-impairing or [[amnesia|amnestic]]<ref name=not_diazepam>{{cite journal | first = T | last = Seppala | coauthors = Palva E, Mattila MJ, Korttila K, Shrotriya RC | year = 1980 | title = Tofisopam, a novel 3,4-benzodiazepine: multiple-dose effects on psychomotor skills and memory. Comparison with diazepam and interactions with ethanol | journal = Psychopharmacology (Berlin) | volume = 69 | issue = 2 | pages = 209–18 | pmid = 6109345 | doi = 10.1007/BF00427652}}</ref> 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]]).<ref name=curiouser_and_curiouser>{{cite journal | first = V. | last = Saano | year = 1986 | title = Tofizopam selectively increases the action of anticonvulsants | journal = Medical Biology | volume = 64 | issue = 4 | pages = 201–6 | pmid = 3023768}}</ref> Tofisopam is indicated for the treatment of anxiety and [[alcohol withdrawal]], and is prescribed in a dosage of 50 – 300&nbsp;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.<ref>http://www.biam2.org/www/Sub1469.html</ref>

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]],<ref name=dtfp_ibs>{{cite web | author = Vela Pharmaceuticals | year = 2005 | url = http://www.velapharm.com/news/press050104.html | title = Vela Announces Positive Phase 2 Results for Dextofisopam in Treating Irritable Bowel Syndrome - IBS: Results Show Effects of Dextofisopam Both in Women and in Men | work = VelaPharm - News | accessdate = 21 February 2006}} {{Dead link|date=October 2010|bot=H3llBot}}</ref> with moderate efficacy demonstrated in clinical trials so far.<ref>Leventer SM, Raudibaugh K, Frissora CL, Kassem N, Keogh JC, Phillips J, Mangel AW. Clinical trial: dextofisopam in the treatment of patients with diarrhoea-predominant or alternating irritable bowel syndrome. ''Alimentary Pharmacology and Therapeutics''. 2008 Jan 15;27(2):197-206. PMID 17973974</ref>

Tofisopam has been shown to act as an inhibitor of the liver enzyme [[CYP3A4]],<ref>Tóth M, Bajnógel J, Egyed A, Drabant S, Tömlo J, Klebovich I. Effect of tofisopam on CYP3A4 enzyme activity on human recombinant 3A4 supersome. (Hungarian) ''Acta Pharmaceutica Hungarica''. 2005;75(4):195-8. PMID 16711396</ref> and this could potentially cause dangerous drug interactions with other medications metabolised by this enzyme,<ref>Drabant S, Tóth M, Bereczki A, Bajnógel J, Tömlö J, Klebovich I. Effect of tofisopam on the single-oral-dose pharmacokinetics and pharmacodynamics of the cyp3a4 probe drug alprazolam. ''European Journal of Clinical Pharmacology''. 2006 Jul;62(7):587-8. PMID 16791582</ref><ref>Tóth M, Drabant S, Varga B, Végso G, Cseh A, Szentpéteri I, Klebovich I. Tofisopam inhibits the pharmacokinetics of CYP3A4 substrate midazolam. ''European Journal of Clinical Pharmacology''. 2008 Jan;64(1):93-4. PMID 17989974</ref> although the clinical significance of these findings remains unclear.

==See also==

*[[Benzodiazepine]]

==References==

==External links==

[[fr:Tofisopam]]

[[hu:Tofizopám]]

[[ja:トフィソパム]]

[[pl:Tofisopam]]

[[ru:Тофизопам]]