The action of the cinchona and certain other alkaloids in bird malaria. Pt. 2 / by G.A.H. Buttle, T.A. Henry and J.W. Trevan.

  • Buttle, G. A. H. (Gladwin Albert Hurst), 1899-1983.
Date:
[1934]
Catalogue details

Licence: Public Domain Mark

Credit: The action of the cinchona and certain other alkaloids in bird malaria. Pt. 2 / by G.A.H. Buttle, T.A. Henry and J.W. Trevan. Source: Wellcome Collection.

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    The final decision as to which is the most active must rest on clinical evidence, which is notoriously difficult to assess. It is however, with the present evidence, unjustifiable to assume that all the crystallisable alkaloids are of equal value. The same order can be deduced from the results of previous workers [Goodson et al., 1930; Giemsa et al., 1926; Giemsa and Oesterlin, 1933] except as regards quinidine. Goodson et al. [1930] obtained results, which suggest that quinidine has a higher activity than that now assigned to it. The number of birds on which quinidine is given its place, is small, owing to the fact that some died during the experiment. It is probable that 5 mg. daily is too toxic a dose for quinidine, though the large majority of canaries survive these doses of the other alkaloids. In this respect our canaries are less sensitive than those used by Giemsa. The apparent difference cannot be explained by any difference in purity of the alkaloids used. The point is however being further investigated together with the proper place of cinchonine. The effect of hydrogenation is astonishingly different for different alkaloids. For quinine and possibly quinidine, hydrogenation increases the activity; for cinchonine the effect is probably to diminish the activity. No possible explana¬ tion can be offered and yet another instance of lack of correspondence between biological activity and chemical structure must be left on record. Table A. Di hydroquinine Quinine Dihydroquinidine Cinchonidine 1-2 1 0-5-1 About 0-5 Quinidine About 0-5* Cinchonine Less than 0-2 Dihydrocinchonine ,, Dihydrocinchonidine ,, * Further experiments with the pure alkaloids suggest that this is an overestimate rather than an underestimate of the relative activity of quinidine. Modified cinchona alkaloids. In the previous paper it was shown that although quitenine is itself inactive it recovers antimalarial activity on esterification; this activity is slight for the methyl and ethyl esters and only becomes well- marked in the butyl and amyl esters. Observations with two of these esters have been repeated with the results recorded in Table B, which are given in a form readily comparable with those of Goodson et al. These results are interesting in two ways; (1) they are both positive, whereas in the former more extensive series negative results were occasionally obtained with each substance; (2) the improvement in activity from ethyl to amyl is not so well-marked as in the previous experiments. These alkylquitenines are some¬ what readily hydrolysed, and it is suggested that the apparent variation in antimalarial activity is caused by varying capacity for hydrolysing the drugs shown by different canaries. Less variable results would probably be obtained by intravenous injection, a method not well suited for use with canaries. Certain of the cinchona alkaloid “chlorides” being available for other pur¬ poses, the opportunity was taken to try them in bird malaria. Quinine chloride, dihydro quinine chloride and cinchonidine chloride all proved inactive in six daily doses of 5 mg. as was to be expected from the recorded inactivity of quinine chloride [Giemsa et al., 1926]. It is however of interest to note that whilst in the authors’ experiments no difficulty was experienced in giving doses of 5 mg. of these chlorides, Giemsa was only able to give 1*5 mg., a further example of variability in canaries. The disappearance of activity as a result of replacing the —CHOH— group by —CHC1— is a striking example of the im¬ portant part played by this group in this set of alkaloids, activity disappearing