Sulbutiamine/ja

Sulbutiamine/ja

Clinical data
Trade names	Arcalion, Enerion
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	A11DA02 (WHO)
Pharmacokinetic data
Elimination half-life	5 hours
Excretion	Renal
Identifiers
IUPAC name [4-[(4-amino-2-methyl-pyrimidin-5-yl)methyl-formyl-amino]-3-[2-[(4-amino-2-methyl-pyrimidin-5-yl)methyl-formyl-amino]-5-(2-methylpropanoyloxy)pent-2-en-3-yl]disulfanyl-pent-3-enyl] 2-methylpropanoate
CAS Number	3286-46-2 N
PubChem CID	71124
ChemSpider	16736830 Y
UNII	42NCM1BW43
KEGG	D01319 Y
Chemical and physical data
Formula	C32H46N8O6S2
Molar mass	702.89 g·mol−1
3D model (JSmol)	Interactive image
SMILES Nc2nc(C)ncc2CN(C=O)C(/C)=C(/CCOC(=O)C(C)C)SSC(/CCOC(=O)C(C)C)=C(/C)N(C=O)Cc1cnc(C)nc1N
InChI InChI=1S/C32H46N8O6S2/c1-19(2)31(43)45-11-9-27(21(5)39(17-41)15-25-13-35-23(7)37-29(25)33)47-48-28(10-12-46-32(44)20(3)4)22(6)40(18-42)16-26-14-36-24(8)38-30(26)34/h13-14,17-20H,9-12,15-16H2,1-8H3,(H2,33,35,37)(H2,34,36,38)/b27-21-,28-22- Y Key:CKHJPWQVLKHBIH-ZDSKVHJSSA-N Y
NY (what is this?)  (verify)

スルブチアミン（Sulbutiamine、商品名Arcalion、Enerion）は、チアミン（ビタミンB₁）の合成誘導体である。フランスでは、虚弱や疲労の症状の治療に用いられる。 また、栄養補助食品としても販売されている。 スルブチアミンは、有用なチアミン誘導体を開発する努力の一環として日本で発見された。

Medical use

Sulbutiamine is used to treat asthenia (symptoms of fatigue or weakness), though is not clear if it is effective in alleviating tiredness. It is also used to treat thiamine deficiency and poor concentration. Being a potent cholinergic anxiolytic , Sulbutiamine is a popular nootropic, with users reporting enhanced memory, focus and improved mood and motivation. Endurance athletes may use it to try to enhance their performance.

Adverse effects

Adverse effects found in clinical trials are usually limited to headache and gastrointestinal discomfort when high doses are used. While daily use can result in tolerance and paradoxical drowsiness, increasing the dose is strongly discouraged and side effects can include diarrhea, bladder infections, bronchitis, back pain, abdominal pain, insomnia, constipation, gastroenteritis, headache, vertigo, and sore throat.

History

Thiamine

Efforts to develop thiamine derivatives with better bioavailability than thiamine were conducted in the 1950s, mainly in Japan. These efforts led to the discovery of allicin (diallyl thiosulfinate) in garlic, which became a model for medicinal chemistry efforts to create other thiamine disulfides. The results included sulbutiamine, fursultiamine (thiamine tetrahydrofurfuryl disulfide) and benfotiamine. These compounds are hydrophobic, easily pass from the intestines to the bloodstream, and are reduced to thiamine by cysteine or glutathione.

It was first marketed in France by Servier in 1973 under the brand name Arcalion. The drug registration went through a validation procedure in France in the 1980s, which found that the use for treatment of fatigue was not supported by data. In January 1989, 100 mg tablet doses were discontinued in favour of 200 mg tablets.

Research

Because thiamine deficiency causes problems with memory and other cognitive functions, thiamine and analogs like sulbutiamine have been studied in clinical trials in the 1980s and 1990s for age-associated cognitive decline.

Sulbutiamine has been explored in clinical trials as a potential treatment for chronic fatigue syndrome. Studies have also been undertaken to assess its impact on reversing age-related changes in the circadian system.

The pharmacology of sulbutiamine has been studied in various mice and rats; as of 2014 it appeared that sulbutiamine might be more effective in raising thiamine phosphate levels in the brain than benfotiamine and fursultiamine, but this has not been fully verified. University of Oxford studies indicate that it helps prevent apoptotic cell death, caused by trophic factor deprivation, in retinal ganglion cells.

In an uncontrollled clinical trial, sulbutiamine was reported to be effective in reducing fatigue in patients with multiple sclerosis.

See also

• Vitamin B₁ analogue
• Pyritinol