الكاتب: Multiple References

When both salts were given subcutaneously to mice, increase in dose of the chloride beyond that involving administration of dispersed solid as well as solution did not raise the toxicity significantly, and at such doses the chloride was much less toxic subcutaneously or intramuscularly than the methylsulphate. There was no difference in toxicity after intravenous administration. When the chloride was given subcutaneously to mice in doses of 25 mg./kg. it conferred protection against subsequent infection by T. congolense for at least six weeks. The same dose given by slow intravenous injection conferred protection only for a few days. In the rabbit it was shown that a subcutaneous deposit of the chloride became encapsulated and could be detected for several weeks after the injection. Removal of the residue resulted in loss of prophylactic activity. Curd and Davey (1950) thought that these and analogous results could be ascribed to the very different solubilities in water of the chloride and methylsulphate, which are of the order of 0.1 and 30 per cent (w/v) respectively. They suggested that the dissolved part of the chloride was rapidly absorbed, and that the undissolved part remained behind to form a reservoir from which slow seepage into the blood stream could occur. They also suggested that the prophylactic activity of the methylsulphate, which is less than that of the chloride, might be due to its partial precipitation at the injection site by interaction with body anions such as chloride. Persistence owing to formation of a subcutaneous reservoir of sparingly soluble or slowly absorbed material was first demonstrated by Browning and co-workers (Browning, Cohen, Cooper, Ellingworth, and Gulbransen, 1933; Browning and Gulbransen, 1934), who were able to detect a highly coloured styrylquinoline derivative at the injection site for more than a year after it was administered, and to associate this phenomenon with prolonged prophylactic action against trypanosomal infections.