Experiments on antimony compounds used in the treatment of Bilharzia disease and kala-azar / by W.H. Gray and J.W. Trevan.

  • Gray, William Herbert.
Date:
[1931]
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Licence: Public Domain Mark

Credit: Experiments on antimony compounds used in the treatment of Bilharzia disease and kala-azar / by W.H. Gray and J.W. Trevan. Source: Wellcome Collection.

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    of antimony, in which antimony is attached directly, and not as in the “ emetic ” type of substance through oxygen, to carbon, marked the third and most successful stage. These do not give rise to the pneumonia, thought to be due to the liberation of antimony trioxide by the serum alkali, which is the most frequent cause of death during treatment with tartar emetic ; the death rate has been reduced by their use to less than 5 per cent., and the period of treatment shortened from the eight to ten weeks required with tartar emetic to a few days. The first of them to achieve clinical success in India was “ urea stibamine,” prepared by Brahmachari (1922) by the action of urea upon para-amino- phenylstibinic acid (stibanilic acid). Its nature, however, was the subject of controversy. The progress of chemotherapy depends upon exact knowledge of the chemical constitution of drugs which prove to be clinically useful, and for this reason the authors (1931) thought it desirable to investigate “ urea stibamine,” and have shown that it is a mixture and identified its constituents. The problem involved the chemical and pharmacological examination of “ urea stibamine ” itself, and comparison of its trypanocidal activity with that of those constituents prepared by other methods in a pure condition. Stibanilic acid (III) is the parent substance of all the organic compounds of antimony which have come into use in medicine. It is a derivative of aniline (I), formed by substituting the antimonic acid residue-SbO(OH)2 for a hydrogen atom :— H—N—H CH3CONH H—N—H ch3co-nh C C C c / ^ / w / V / w H—C C—H H—C C—H H—C C—H H—C C—H II 1 II 1 II 1 II 1 X 1 o o X H—C C—H H—C C—H H—C C—H \ // \ '// \ // \ // c C C C H H HO—Sb—OH 11 HO—Sb—OH II 0 0 I. II. III. IV. Introduction of an acetyl group, CH3 -CO-, as in the formation of acetanilide (II) from aniline, decreases the toxicity in both instances and gives the acid (IV), of which the sodium salt, known as “ stibacetin,” was the first organic antimony compound to be tried clinically. With this, good results were obtained in the treatment of kala-azar in Italy, but not in India. A chlorinated modification,