Arsphenamine syphilis

Under the intellectual leadership of Paul Ehrlich, the dye industry provided arsphenamine, the first effective agent against syphilis. Syphilis is an infectious disease spread by sexual contact. It is caused by the spirochete Treponema pallidum. Syphilis runs various courses over many years and can result in death if not treated. Penicillins are now the dmgs of choice for syphilis. Chemists discovered two other medicinal agents in the early years of the twentieth century tryparsamide for trypanosomiasis, a parasitic disease, and oxophenarsine, also for syphilis. 

The compound arsphenamine is also called compound 606 because it was the 606th arsenic compound that Paul Ehrlich (1854-1915) had synthesized for use in treating diseases. His assistant found this compound to be effective as a treatment for syphilis. Ehrlich also coined the word chemotherapy. ... 

Paul Ehrlich s "magic bullet" for syphilis (arsphenamine, Salvarsan) was an arsenical. 

The toxicity of arsenic has been put into practical use in medicine. Ehrlich in 1909 developed Salvarsan, the trade name for arsphenamine (1), which was the first modem chemotherapeutic agent effective in the treatment of syphilis, which was eventually phased out by better organoarsenicals and latter by penicillin. Some specialist arsenical dmgs are still the treatment of choice for amoebic infections like glycobiarsol (2). ... 

Arsenic was, without doubt, important in the successful treatment of S5q>hilis. The drug Salvarsan (arsphenamine) was discovered by Paul Erhlich during a systematic study of arsenic compounds for a potential cure for syphilis. Salvarsan is a synthetic organic chemical that contains arsenic he had tried more than 600 chemicals when he happened on this one. His quest was based on the behef that he could find a substance that was selectively toxic to the organism that causes syphilis (a spirochaete) but less toxic to the patient, a magic bullet . Only recently, arsenic trioxide (the form of arsenic commonly used for homicide) was licensed by the... 

Arsphenamine has been found to be extremely valuable. Its greatest use is in the treatment of syphilis the drug attacks the micro-organism responsible for this disease, Spirocheta pallida. It has also been useful in the treatment of some other diseases. At the present time it seems to be in the process of being superseded by penicillin (which we shall discuss below) in the treatment of syphilis. 

Ehrlich later synthesized another compound, neoarsphenamine. which is somewhat superior to arsphenamine for the treatment ol syphilis. It is closely related in structure, differing only in having a more complicated side chain in place of two of the amino groups of the molecule. 

Arsphenamin was the first drug substance with thermotropic mesomorphism to be therapeutically used as Salvarsan during the first half of the nineteenth century. The drug is effective against microorganisms and thus offered for the first time an efficient therapy of veneral diseases such as syphilis. Nowadays, it has been replaced by antibiotics with less serious side effects. 

Arsenic has a special place in the history of modern medicine. In 1910, German biologist Paul Ehrlich (1854—1915) invented the first drug that would cure syphilis, a sexually transmitted disease. This drug, called salvarsan, is a compound of arsenic. Its chemical name is arsphenamine. 

Chemotherapy may be said to have begun when Ehrlich developed his arsphenamine treatment of syphilis (1910), the so-called magic bullets that killed microorganisms with minimum damage to the host. This practice has been broadly applied to cancer therapy in recent years but without positive results. Another significant event was Funk s discovery (1911) of the ability of certain plant products to cure a disease called beri-beri these soon were named vitamins. Their classification, metabolic functions, and curative properties were established by many researchers, including McCollum, Szent-Gyorgyi, Sherman, and R. J. Williams (B complex). 

At the invention of modem drug discovery, Paul Ehrlich screened just over 600 synthetic compounds to discover arsphenamine (Salvarsan), a novel treatment for syphilis. With advances in screening technology, researchers can now routinely test millions of compounds in protein-based... 

Early in the twentieth century, Paul Ehrlich introduced the arseno dye salvarsan (Arsphenamine) for the treatment of syphilis. Salvarsan was the first synthetic anti-infective drug and thus represented a major breakthrough despite its toxicity. 

The period of systematic development of arsenic drugs commenced at the end of the nineteenth century, and brought about some remarkable improvements in medicine. Arsenic compounds, administered as Fowler s solution (potassium arsenite), Donovan s solution (arsenic iodide) or de Valagin s solution (arsenic trichloride), were employed to treat rheumatism, arthritis, asthma, malaria, trypanosome infections, tuberculosis, and diabetes. N-Acetylar-sanilic acid (C8H10ASNO4), and primarily Sal-varsan (arsphenamine, C12H14AS2CI2N2O2) were discovered by Ehrlich in 1909, and remained in use to treat syphilis until the advent of antibiotics in the 1940s (Baumler... 

The synthetic substance arsphenamine was used, in 1909, by the German bacteriologist Paul Ehrlich (1854-1915) as a therapeutic agent against syphilis. This application is taken as having founded the study of chemotherapy, the treatment of disease by the use of specific chemicals. 

Yet this run of bad luck was suddenly to change, for in 1910 a discovery of utmost significance was made, namely the anti-syphilitic drug arsphenamine (6.3), whose laboratory code number had been 606 (Ehrlich and Hata, 1910). It happened as follows. In 1905 Schaudinn had discovered that the causative organism of syphilis was a highly motile bacterium (a spirochaete) which he... 

Fig. 6.2 Paul Ehrlich (1854-1915) and Sahachiro Hata (1873-1938), who together discovered the curative action of arsphenamine ( Salvarsan ) in syphilis.

The synthesis of arsphenamine was reported by Ehrlich and Bertheim (1912) and it was patented and then manufactured by the firm, Hoechst (DRP 224 953), and sold by them under the name Salvarsan . The initial announcement of a cure for syphilis was taken up by the newspapers, and Ehrlich became a world celebrity overnight. This fame gave him little pleasure, for he had worries that arose from the discovery. For example, arsphenamine was oxidized in the air to a more toxic product, now known to be oxophenarsine 6.4) a much more selective and desirable drug, and one that would in time replace arsphenamine (see Section 6.2). However, at that time, the uncontrolled oxidations were causing deaths, so that Ehrlich decided that arsphenamine must be issued only as single doses, and in sealed tubes from which all oxygen had been removed. He also issued directions for the preparation of solutions in sterile distilled water, neutralization, and intravenous injection without delay. These directions were often departed from, and the resulting disasters attracted unfortunate publicity. Ehrlich later introduced neoarsphenamine ( 914 ), a more soluble derivative. 

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