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Arsphenamine

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Title: Arsphenamine  
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Subject: Paul Ehrlich, Sahachiro Hata, Antibiotics, Syphilis, Timeline of antibiotics
Collection: Amines, Antibiotics, German Inventions, Organoarsenic Compounds, Paul Ehrlich, Phenols, Syphilis
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Arsphenamine

The structure of Arsphenamine has been proposed to be akin to the azobenzene (A), but mass spectral studies published in 2005 suggest[1] it is actually a mixture of the trimer B and the pentamer C.

Arsphenamine, also known as Salvarsan or compound 606, is a chemotherapeutic agent.

Contents

  • History 1
  • Structure 2
  • See also 3
  • References 4

History

First synthesized in 1907 in lead compound through systematic chemical modifications, the basis for nearly all modern pharmaceutical research. The target of Arsphenamine is the bacterium Treponema pallidum, a spirochete that causes syphilis.

Arsphenamine was originally called "606" because it was the sixth in the sixth group of compounds synthesized for testing; it was marketed by mercury compounds that had been used previously. It was distributed as a yellow, crystalline, hygroscopic powder that was highly unstable in air.[6] This significantly complicated administration, as the drug had to be dissolved in several hundred milliliters of distilled, sterile water with minimal exposure to air to produce a solution suitable for injection. Some of the side effects including rashes, liver damage, and risks of life and limb[7] attributed to Salvarsan were thought to be caused by improper handling and administration, causing Ehrlich, who worked assiduously to standardize practices, to observe, "the step from the laboratory to the patient's bedside ... is extraordinarily arduous and fraught with danger." [4]

Ehrlich's laboratory developed a more soluble (but slightly less effective) arsenical compound, Neosalvarsan (neoarsphenamine), which was easier to prepare, and it became available in 1912. Less severe side-effects such as nausea and vomiting were still common. An additional problem was that both Salvarsan and Neosalvarsan had to be stored in sealed vials under a nitrogen atmosphere to prevent oxidation. These arsenical compounds were supplanted as treatments for syphilis in the 1940s by penicillin.[8]

After leaving Erlich's laboratory, Hata continued parallel investigation of the new medicines in Japan.[9]

Structure

In terms of its molecular structure, Salvarsan's has long been assumed to feature an As=As double bond, akin to the N=N linkage in azobenzene. However, in 2005, an extensive mass spectral analysis Salvarsan was shown to have As-As single bonds, not As=As double bonds. Furthermore, the drug is a mixture consisting of cyclo-As3 and cyclo-As5 species.[1][4][10]

See also

References

  1. ^ a b Lloyd NC, Morgan HW, Nicholson BK, Ronimus RS (2005). "The composition of Ehrlich's salvarsan: resolution of a century-old debate". Angew. Chem. Int. Ed. Engl. 44 (6): 941–4.  
  2. ^ Gibaud, Stéphane; Jaouen, Gérard (2010). "Arsenic - based drugs: from Fowler's solution to modern anticancer chemotherapy". Topics in Organometallic Chemistry. Topics in Organometallic Chemistry 32: 1–20.  
  3. ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726818/
  4. ^ a b c "Salvarsan".  
  5. ^ In Germany, it was the practice to designate compounds by their development number. Another compound known commonly in Germany by its number is parathion, which was the 605th compound to be developed in search for insecticide. It is commonly known as E605 (E stands for Entwicklungsnummer (German for "development number"))
  6. ^ "A Handbook of Useful Drugs".  
  7. ^ http://archive.protomag.com/assets/paul-ehrlich-and-the-salvarsan-wars
  8. ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790789/
  9. ^ Izumi, Yoshio; and Isozumi, Kazuo (2001). "Modern Japanese medical history and the European influence" (free download pdf). Keio Journal of Medicine 50 (2): 91–99.  
  10. ^ http://www.rsc.org/chemistryworld/2013/04/salvarsan-podcast
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