Sulbutiamine

Last updated
Sulbutiamine
Sulbutiamine.svg
Sulbutiamine 3D spacefill.png
Clinical data
Trade names Arcalion, Enerion
AHFS/Drugs.com International Drug Names
Routes of
administration
Oral
ATC code
Pharmacokinetic data
Elimination half-life 5 hours
Excretion Renal
Identifiers
  • [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
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard 100.019.944 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C32H46N8O6S2
Molar mass 702.89 g·mol−1
3D model (JSmol)
  • 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=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- Yes check.svgY
  • Key:CKHJPWQVLKHBIH-ZDSKVHJSSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Sulbutiamine (brand names Arcalion, Enerion) is a synthetic derivative of thiamine (vitamin B1). In France, it is used to treat symptoms of weakness or fatigue. It is also sold as a dietary supplement. Sulbutiamine was discovered in Japan as part of an effort to develop useful thiamine derivatives.

Contents

Medical use

Sulbutiamine is used to treat asthenia (symptoms of fatigue or weakness), [1] though is not clear if it is effective in alleviating tiredness. [2] It is also used to treat thiamine deficiency and poor concentration. Being a potent cholinergic anxiolytic [ citation needed ], 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. [3] [4]

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. [5]

History

Thiamine Thiamin.svg
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. [6] :302 [7]

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. [2] In January 1989, 100 mg tablet doses were discontinued in favour of 200 mg tablets. [8]

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. [9]

Sulbutiamine has been explored in clinical trials as a potential treatment for chronic fatigue syndrome. [5] Studies have also been undertaken to assess its impact on reversing age-related changes in the circadian system. [10]

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. [6] :303 University of Oxford studies indicate that it helps prevent apoptotic cell death, caused by trophic factor deprivation, in retinal ganglion cells. [11]

In an uncontrollled clinical trial, sulbutiamine was reported to be effective in reducing fatigue in patients with multiple sclerosis. [12]

See also

Related Research Articles

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

Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thiamine are required for some metabolic reactions, including the breakdown of glucose and amino acids.

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Wernicke-Korsakoff syndrome (WKS) is the combined presence of Wernicke encephalopathy (WE) and Korsakoff syndrome. Due to the close relationship between these two disorders, people with either are usually diagnosed with WKS as a single syndrome. It mainly causes vision changes, ataxia and impaired memory.

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

Allicin is an organosulfur compound obtained from garlic. When fresh garlic is chopped or crushed, the enzyme alliinase converts alliin into allicin, which is responsible for the aroma of fresh garlic. Allicin is unstable and quickly changes into a series of other sulfur-containing compounds such as diallyl disulfide. Allicin is an antifeedant, i.e. the defense mechanism against attacks by pests on the garlic plant.

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<span class="mw-page-title-main">Nootropic</span> Compound intended to improve cognitive function

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

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<span class="mw-page-title-main">Zopiclone</span> Hypnotic medication

Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone increases the normal transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system, via modulating GABAA receptors similarly to the way benzodiazepine drugs do.

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

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

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<span class="mw-page-title-main">Benfotiamine</span> Thiamine analogue

Benfotiamine is a synthetic, fat-soluble, S-acyl derivative of thiamine that is approved in some countries as a medication or dietary supplement to treat diabetic sensorimotor polyneuropathy. Benfotiamine was developed in late 1950s in Japan.

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<span class="mw-page-title-main">Fosazepam</span> Benzodiazepam

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

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References

  1. "Fiche info - Araclion 200 mg" (in French). Base de données publique des médicaments: ANSM of HAS et UNCAM. Retrieved 28 January 2018.
  2. 1 2 Rane W (1997). "High Cost, Low Efficiency Medicines". Economic and Political Weekly. 32 (51): 3251. JSTOR   4406199.
  3. Kazlauskas R (2010). "Advances in sports drug testing: an overview". Drug Testing and Analysis. 2 (11–12): 523–5. doi: 10.1002/dta.251 . PMID   21204284. Open Access logo PLoS transparent.svg
  4. Starling-Soares B (2020). "Role of the Synthetic B1 Vitamin Sulbutiamine on Health". Nutr Metab. 2020: 1–9. doi: 10.1155/2020/9349063 . PMC   7210561 . PMID   32399290. Open Access logo PLoS transparent.svg
  5. 1 2 Alraek T, Lee MS, Choi TY, Cao H, Liu J (October 2011). "Complementary and alternative medicine for patients with chronic fatigue syndrome: a systematic review". BMC Complementary and Alternative Medicine. 11: 87. doi: 10.1186/1472-6882-11-87 . PMC   3201900 . PMID   21982120.
  6. 1 2 Bettendorff L (2014). "Chapter 7 - Thiamine". In Zempleni J, Suttie JW, Gregory JF, Stover PJ (eds.). Handbook of vitamins (Fifth ed.). Hoboken: CRC Press. pp. 267–324. ISBN   9781466515574.
  7. Volvert ML, Seyen S, Piette M, Evrard B, Gangolf M, Plumier JC, Bettendorff L (June 2008). "Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives". BMC Pharmacology. 8: 10. doi: 10.1186/1471-2210-8-10 . PMC   2435522 . PMID   18549472.
  8. "Economic and Political Weekly, Volume 32". Sameeksha Trust. 1997. p. 3251.
  9. Riedel WJ, Jolles J (April 1996). "Cognition enhancers in age-related cognitive decline" (PDF). Drugs & Aging. 8 (4): 245–74. doi:10.2165/00002512-199608040-00003. PMID   8920174. S2CID   22677895.
  10. "Animal Behavior Abstracts, Volume 23". Cambridge Scientific Extracts. 1995. p. 139.
  11. Issues in Neuroscience Research and Application: 2011 Edition. Scholarly Editions. 2011. p. 529. ISBN   9781464963605.
  12. Sevim S, Kaleağası H, Taşdelen B (August 2017). "Sulbutiamine shows promising results in reducing fatigue in patients with multiple sclerosis". Multiple Sclerosis and Related Disorders. 16: 40–43. doi:10.1016/j.msard.2017.05.010. PMID   28755683.