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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    introduire doivent satisfaire et quelle doit etre leur composition et (b) quelle est la dose a laquelle il faut les administrer pour le succes soit assure” [Van der Sleen and Drossart Lulofs, 1931]. The definition of “totaquina” allows considerable latitude in the relative proportions of the various cinchona alkaloids present, and in consequence there is much variation in this respect in commercial “totaquina,” as the following analyses show: Table I. Composition of “totaquina Type I Type II Type III o/ * /o %t o/ * /o Quinine 32-5 15-3 17-0 Cinchonidine 34-2 5-7 24-0 Quinidine — 5-2 100 Cinchonine 20-1 55-4 230 Total crystallisable alkaloids 86-8 81-6 74-0 Amorphous alkaloids 9-9 13-4 170 Moisture 2-6 1-9 5-0 Ash 0-2 2-1 40 * Manufacturer’s analysis. f Analysis by Mr J. A. Goodson. It is obvious that if there is a marked difference in the action of, say quinine and cinchonine, the therapeutic values of “totaquina” of types I and II will be different and some evidence for this view has already been brought forward as a result of trials of these two types in bird malaria [Giemsa, 1932] and in human malaria [Malaria Commission, League of Nations, 1933]. It appeared to the authors that definite quantitative evidence on this matter could best be obtained by comparative trials of pure specimens of the individual alkaloids in bird malaria. The four primary cinchona alkaloids have been purified by processes de¬ scribed later, and a method of controlling these processes, so far as the elimination of the dihydro-bases is concerned has been devised. From the primary bases the pure dihydro-bases have been prepared by catalytic hydrogenation. As there was no certainty that any of these eight alkaloids had been obtained pure previously the principal constants of each have been determined and are recorded and compared with the best of the known previous determinations in Tables II, III and IV. The biological trials gave results which are summarised in Table A. The figures represent the dose of quinine necessary to produce the same amount of protection as unit dose of the other alkaloids. The figures are only approximate, but the authors think that (a) the distinction between quinine and dihydro¬ quinine is certain, (6) that dihydroquinidine, cinchonidine and quinidine are definitely less active than quinine and (c) that dihydro cinchonine and dihydro- cinchonidine form a group of much lower activity than any of the others. The samples of quinidine and cinchonine used were not the purest available; the quinidine contained 1-8 % of dihydroquinidine and cinchonine 1-4 % of dihydro¬ cinchonine. Trials with pure alkaloids were spoilt by the outbreak of a B. gaertner epidemic in the stock of canaries, but it will be seen that the removal of these amounts of the dihydro-alkaloids would not affect the order of activity given in the table. It is not claimed that the order in which the drugs are arranged in this table necessarily represents the order of antimalarial activity in man. But it is logical to assume that, if the alkaloids differ so much in their activity on the parasite experimented with, they will not be of equal therapeutic value in man.