FOUNDATIONS OF MODERN TROPICAL MEDICINE 27 



suggested in the treatment of trypanosomiasis, but in man the results have 

 not been so successful as in the lower animals. 



Mercury was first introduced in 1902 for the treatment of sleeping sickness 

 by Low and Castellani, using intravenous injection of Baccelli's sublimate 

 solution (hydrargyri perchloridi, cio gramme; sodii chloridi, 0*50 gramme; 

 aquae destillatse, loo-oo c.c. ; i to 4 c.c. per intravenous injection), in associa- 

 tion with arsenic and quinine by the mouth. A fall of the temperature was 

 observed in some cases, but the fatal course of the disease was not influenced. 

 Moore, Nierenstein, and Todd have used mercury and atoxyl in combination 

 or alternation, with the idea that mercury might act upon the latent form 

 of the trypanosome, while atoxyl would influence the active form. In man 

 this combined treatment has apparently not given any better results than 

 atoxyl alone. This combined treatment, consisting of atoxyl and an 

 inorganic salt of arsenic such as orpimet't, has been recommended by 

 Laveran and Thiroux, and has already been used in man with good results. 

 The orpiment should be given in pills, in the dose of 2 grains of orpiment two 

 or three times daily. The administration of orpiment frequently causes 

 diarrhoea. Thiroux therefore incorporates in the orpiment pills some opium. 



Ehrlich observed that the aromatic compounds of tervalent arsenic were 

 more ef&cacious in attempts to kill protozoan parasites, and after 605 attempts 

 in 1909 he evolved Salvavsan, or 606, also known as Kharsivan and Arsenobillon, 

 which is a pale yellow powder soluble in dilute hydrochloric acid or aqueous 

 sodium hydroxide or carbonate. Its formula is the hydrochloride of 3 : 3*- 

 diamino -4 : 4'-di-hydroxy arseno-benzene — i.e. .* — 



As = As 



HCl, NH, 



NHo, HCl, 2H0O 



OH 



OH 



On account of its phenolic and feebly basic properties, Salvarsan fails to 

 give neutral salts, and the free base is very insoluble in water or in normal 

 saline solution ; therefore an approximately neutral solution has to be prepared 

 immediately before use, which is inconvenient, and led to the search for a 

 compound with soluble salts giving a neutral reaction in solution. Such a 

 preparation had been foreshadowed by Ehrlich's 418 Spirarsyl, or the sodium 

 salt of arsenophenylglycine, which was the most successful of the arsenic 

 compounds prior to Salvarsan. 



It was found that Salvarsan dihydrochloride could be made to produce a 

 compound called Ehrlich's 914, or Neosalvarsan, also called Neokharsivan, 

 Novarsenobillon, Novarsenobenzol, or Sodium 3 : 3*-diamino-4 : 4*-dihydroxy- 

 arsenobenzene-N-methylene sulphurate : — 



As = 



As 



NHo 



OH 



NH CHo. O. SONa 



OH 



This is a pale yellow powder, with (commercially) generally small proportions 

 of inorganic salts. It is soluble in water and the solution is quite n-^utral, 

 but its arsenical content is lower than that of Salvarsan, and hence its average 

 dose is larger, and the efficacy of the preparation should be tested by intra- 

 venous injections into rabbits. 



Galyl, discovered by Mouneyrat, is 4 : 4'-dihydroxyarsenobenzene-3 : 3*- 

 phosphamic acid, and forms a neutral solution when added to aqueous sodium 

 carbonate, and is useful in syphilis and also kills spirochaetesand trypanosomes . 

 It is very slightly toxic. Ludyl is a complex disulphonamide discovered as 



