It is obtainable as the hydrochloride, under the trade name of Salvarsan, but before use it is generally transformed into the sodium salt by dissolving it in soda.* These solutions do not keep well.1 A great many favourable reports have been published concerning the action of this compound, which has a very low toxicity. Its action in vitro is very weak, and it therefore presumably undergoes some change in the organism.2 Organic Antimony Compounds.-The trypanocidal action of antimony, compared with that of arsenic, has been discussed in the first section of this chapter. Unfortunately no antimony preparations analogous to the more successful of the arsenic compounds have yet been obtained, and none of the compounds which have been tried up to the present fulfil all the conditions necessary for a really efficient trypanocide. These conditions may be summed up as follows:-8 (1) The compound must be non-irritant, and capable of remaining in perfect solution at the temperature and alkalinity of the tissues. (2) It must act quickly on the trypanosomes before they can acquire a tolerance to the drug. (3) When the trypanosomes have been expelled from the blood by a single full therapeutic dose, there must be no recurrence in the majority of cases within some fixed time, which will depend to some extent on the particular host experimented with, and on the strain of parasites used. Although the arsenic compounds which have been described do not perhaps fulfil the second and third of these conditions, yet the majority of them fulfil the first of these quite admirably, but in the case of antimony, difficulty has been experienced in obtaining derivatives to fulfil even this condition. No compounds containing pentavalent antimony have been of any use, and of the trivalent compounds, those of a similar nature to ordinary tarter emetic (potassium antimonyl tartrate) have appeared to give the best results. Thomson and Cushny have experimented with many compounds of this type derived from various hydroxy acids, and the best results * More recently the hydrochloride itself, in aqueous solutions or oily suspensions, has been used for injection. 1 McDonagh, Lancet (Sept. 3, 1910), 711. 3 Thomson and Cushny, Proc. Roy. Soc., 82 B (1910), 249. 1 Ibid. were obtained with the compounds prepared from tartaric and malic acids HO-CH-COOH HO-CH-COOH Tartaric acid. HO-CH-COOH CH2-COOH Malic acid. The sodium and potassium antimonyl tartrates seemed to be very nearly equal in their efficiency, but ethyl antimonyl tartrate appeared to have some advantage over these alkali salts. None of these compounds are very effective, however, and there is still a great need for a compound which should have a really satisfactory effect in sleeping sickness. Numerous organic compounds of antimony have been prepared, but none of them are likely to be suitable for this purpose, for which, therefore, new compounds will need to be prepared. An investigation on aromatic antimony compounds has been begun by the present author,1 with a view to preparing derivatives which should be of therapeutic value, but the work is as yet in the initial stage. Quite recently, Rountree and Able2 have described some experiments of the treatment of trypanosomiasis with antimony derivatives of thioglycollic acid. The compounds used were sodium antimony thioglycollate Sb 3 and the triamide of antimony thioglycollic acid— S-CH2-CO-NH2 Sb-S-CH2-CO-NH2 S–CH,CO–NH, 1 May, Proc. Chem. Soc., 26 (1910), 142; J. C. S., 97 (1910), 1956. 2 The Journal of Pharmacology (Baltimore), 2 (Oct. 1910), 101–144. 3 Klason and Čarlson, Ber., 39 (1906), 732;` Ramberg, Ber., 39 (1906), 1356. The latter was prepared by allowing antimony oxide to react with this glycollic ester, Sb2O3 + 6HS. CH2. CO. OC2H5 =Sb(-S.CH-CO. OC2H5)3 + 3H2O and transforming the ester so obtained into the amide by means of ammonia in the usual way. The results of the treatment appear to be as good as any that have hitherto been recorded. Quite recently, the injection of finely divided metallic antimony has been advocated as the most satisfactory treatment of trypanosomiasis.1 1 Plimmer and Fry, Proc. Roy. Soc., 81 B (1909), 334; Plimmer, Fry, and Ranken, Proc. Roy. Soc., 83 B (Dec., 1910), 140. CHAPTER XV PURINE DERIVATIVES (DIURETICS) AND URIC-ACID SOLVENTS CAFFEINE, the best known drug of the purine group, is used as a cardiac tonic and cerebral excitant, but in addition it has a diuretic action, as also have other members of the purine group. CHg–N–CO HN-CO do d_N_CH3 со CH-N-C-N CH Although the action of theobromine on the nervous system is far weaker than that of caffeine, its diuretic action is as strong. Both substances suffer from the disadvantage of sparing solubility and small power of resorption. To overcome the drawback of slight solubility, double salts of the sodium derivatives of caffeine and theobromine, with sodium salicylate, benzoate, and acetate, have been prepared. Compounds of sodium theobromine with sodium salicylate and acetate are known as Diuretin and Agurin respectively. The acyl-amino-derivatives of caffeine are said to have a strong diuretic action without the by-effects of caffeine. Mono-acetyl-amino-caffeine, diacetylamino-caffeine, etc., have been prepared.1 According to the investigations of Ach, the dimethyl xanthines have a stronger diuretic action than trimethylxanthine (caffeine). Of these, theobromine (3-7 dimethyl) 1 D. R. P., 139,960. 2 Ach, A. e. P. P., 44 (1900), 319. has the weakest, and theophylline (1-3 dimethyl) the strongest action, but that of paraxanthine (1-7 dimethyl) is the most persistent. Theophylline, which differs from caffeine in having less action on the heart, has been introduced into therapeutics under the name of Theocine, in the form of its compound with sodium acetate. Its practical application is due to a synthetic process, as the natural alkaloid is far too expensive. Theophylline has been synthesized by Fischer and by Traube, the technical preparation being based on the latter method.2 The synthesis of theophylline was carried out by Traube according to the following method. Dimethyl urea was first condensed with cyanacetic acid by means of POCl3, and the resulting compound (II.) converted into the cyclic base (III.) by the action of alkali. This base, when treated with sodium nitrite and acetic acid, yields the isonitroso compound (IV.) CHN–CO |