Arsenic Arsphenamine

Another organic compound of arsenic that is of historical significance was discovered in 1901 by P. Ehrlich. That compound is known as arsphenamine or Salvarsan, which has the structure... 

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. ... 

A virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product or analogous product, or arsphenamine or its derivatives or any other trivalent organic arsenic compound applicable to the prevention, cure or treatment of disease or conditions of human beings... 

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

In 1910, Ehrlich made a historic discovery while investigating one of these arsenicals, the antisyphilitic drug arsphenamine. This particular drug, with the laboratory code designation 606, was so effective in laboratory tests that it was announced as a cure for the dreaded disease and was referred to as a magic bullet . Although the marketed form of the chemical, Salvarsan, ultimately proved to be too toxic for human use, arsphenamine was the opening event in the chemotherapeutic revolution for the treatment of human infections. 

Bismuth arsphenamine sulphonate (Bismarsen , Fig. 9) a yellow powder readily soluble in water, was first prepared by Raiziss in 1924 [70]. Stokes and Chambers [71] were the first to use the drug clinically, giving two injections a week for 14 weeks. Four such courses separated by intervals of a fortnight were administered in all. Nevertheless the effects were slow compared with the arsphenamines, although the tonic effect was greater and the side effects less numerous. Relapses, particularly in the central nervous system (CNS) were more frequent. Consequently, Rayburn and Boyd emphasized the fact that some individuals with neurosyphilis who were intolerant to arsenic in any other form could nevertheless tolerate it in the form of Bismarsen [72]. The low toxicity, the tonic effect, and the ease of administration were the chief advantages in favor of Bismarsen . The other compounds of bismuth with arsenic were not extensively tested in humans. 

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... 

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. 

Use Arsanilates, manufacture of arsenical medicinal compounds such as arsphenamine, veterinary medicine, grasshopper bait. 

The distinction between biopharmaceuticals under the jurisdiction of OBP and ONDG stems from the definition of a biological product in the PHS Act (42 USG 351 [262] (i)) a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or derivative of arsphenamine (or any other tri-valent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings. Biopharmaceuticals under the jurisdiction of OBP are analogous products under this definition. 

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 toxicity of a given arsenical is related to the rate of its clearance from the body and therefore to its degree of accumulation in tissues. In general, toxicity increases in the sequence of organic arsenicals arsenicals contain arsenic covalently linked to a carbon atom, where arsenic exists in the trivalent or pentavalent state. Arsphenamine contains trivalent arsenic sodium arsanilate contains arsenic in the pentavalent form. The organic arsenicals usually are excreted more rapidly than are the inorganic forms. 

The test identifies the substance to be examined as a salt of arsenic(III) or arsenic(V), or a compound containing bound arsenic made available for analysis by chemical degradation. Due to their potential toxicity, arsenic substances must be considered mostly a reminiscence of historical interest. Before World War II a fairly large group of substances containing covalently boimd arsenic was used in the treatment of protozoa. One of the most widely known arsenic drugs was arsphenamine (Figure 3.9.1), which was used in... 

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