CHAPTER 6 



ARSENICALS 



Compounds of arsenic were used in medicine two to three thousand 

 years ago in the Orient and sporadic therapeutic applications have contin- 

 ued through the ages. Meanwhile, arsenic also gained the reputation of a 

 dangerous poison, and during the fifteenth to seventeenth centuries was 

 the principal ingredient of most of the homicidal concoctions of the famous 

 poisoners. Much effort has been expended over the past century to elucidate 

 the mechanisms by which the arsenicals produce their pharmacological 

 and toxicological effects. A detailed chronological account of these develop- 

 ments is unnecessary at this time and would lead us far afield. Instead 

 we shall be content with a few observations signifying the highlights in 

 arsenical research, and then discuss in more detail the history of certain 

 aspects in their appropriate sections. Excellent discussions of the early 

 work may be found in the reviews of Voegtlin et al. (1923), Heffter and 

 Keeser (1927), Keeser (1937), Work and Work (1948), Peters (1955), Doak 

 and Freedman (1960), and Buchanan (1962), and in various textbooks 

 of pharmacology and toxicology. 



The primary stimuli for arsenical research have come from (1) the long 

 history of arsenic as a homicidal poison, (2) the industrial use of the ar- 

 senicals and the resultant exposures to them, (3) the clinical application 

 of the arsenicals in protozoal and neoplastic diseases, and (4) the use of 

 arsenicals in chemical warfare. Arsenical poisoning has been brought 

 about in a variety of ways: wallpaper pigments, cattle dips, insecticides, 

 herbicides, and many different types of industrial exposure have all con- 

 tributed; in addition, toxic reactions during the clinical use of the arsenicals 

 have unfortunately been rather common. Arsenicals have been used at 

 one time or another in almost every type of disease. Inorganic arsenite 

 has its only valid present use in chronic myelocytic leukemia, but has been 

 widely used as a tonic and in a variety of dermatoses (e. g., dermatitis 

 herpetiformis) on the basis of its supposed ability to increase the blood 

 flow through certain tissues, especially the skin, and in intractable bron- 

 chospasm, Arsenite was known to have some effect in trypanosomiasis 

 but its toxicity precluded its use. A major event in the arsenical story 



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