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Salvarsan

 Salvarsan is an arsenic based drug introduced by Paul Ehrlich in 1910 to treat  syphilis, a difuse sexually transmitted disease. His systematic research of specific drugs able to cure particular disease was signing the initial steps of targeted chemotherapy.

Ehrlich was a medical student intrigued by the fact that some aromatic amines and other dyes could accumulate preferentially in specific microbes and provide a staining method. He also predicted that chemists would be able to create substance able to act as "magic bullets," able to exert their action selectively on the parasite present within the human body.

A team constituted by Ehrlich (medical doctor),  Alfred Bertheim (chemist) and Sahachiro Hata (bacteriologist), studied syphilis, an endemic disease that was incurable, and often deadly. At that time, scientists had identified a parasitic bacterium known as Treponema pallidum as the triggering cause of syphilis. The team was convinced that they could be able to identify a magic bullet capable of killing the syphilis-causing bacterium without harming its human host.

Starting from known organic arsenic compounds the team synthetized and evaluated hundreds of related organoarsenic compounds. Eachcompound was tested for biological activity, toxicity, and distribution in rabbits infected with the syphilis-causing bacteria. Compound number 606 (Salvarsan) proved to be the best candidate with a single dose curing the rabbits.

Salvarsan entered rapidly in clinical trials and proved extremelyeffective, particularly when compared with the conventional therapy of mercury salts.  Salvarsan was manufactured by Hoechst, a German chemical company and rapidly became the most widely prescribed drug in the world. This is the first blockbuster drug and remained the most effective drug for syphilis till 1940s, when penicillin became available.

The drug was half successful with respect to the promises, in fact was the proof that synthetic drugs could be produced to treat disease, but was definitely not the magic bullet that Ehrlich dreamed about. Patients with an advanced stage of syphilis failed to respond to the drug; physicians found the drug difficult to handle and administer. Salvarsan dosage form was a powder that doctors had to dissolve in several hundred milliliters of sterilized water and injected intravenously.

Salvarsan administration produced side effects that in part were due to improper handling and administration of the drug. Ehrlich became involved in helping doctors standardize handling and administration of the drug and eventually developed an easier-to-handle derivative with improved water solubility.

 

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