Ergot and its active principles / H.H. Dale.

  • Dale, Henry H. (Henry Hallett), 1875-1968.
Date:
[1912?]
Catalogue details

Licence: Public Domain Mark

Credit: Ergot and its active principles / H.H. Dale. Source: Wellcome Collection.

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    ically identical with it. The failure to recognize this difference, though a small point in itself, had a far-reaching effect on the pharmacological history of the drug. On the basis of clinical results, obtained either with the amorphous alka¬ loid, or with acid solutions of the crystalline alkaloid, in which the amorphous is rapidly formed, Tanret concluded that he had isolated the active alkaloid of ergot. When, however, his alkaloid was subjected to pharmacological experiment by Robert, the crystalline ergotinine as being that of which the purity could be guaranteed, was naturally taken, and injected in fresh solution. Robert rightly concluded that it has practically no activity; and since, according to Tanret, the amorphous alkaloid was chemically identical with it, ergotinine was dismissed as of no pharmacological interest, though it still retained some vogue in practical therapeutics. As a result the chemical investigation of the drug was again given over to the preparation and testing of crude resinous products, though the work of Robert in particular did something towards determining the manner which the specific toxic effects could be recognized. Robert claimed to have separated from ergot three principles, which, though not chemically pure, had each a sep¬ arate and distinct physiological action. One of these, “ergotinic acid,” was ad¬ mittedly of no therapeutic interest, having an action which Robert regarded as related to that of saponins, and need not be further considered. A second, “cor¬ nutin,” a resinous alkaloid preparation, was found to produce convulsions in frogs and mammals, and was regarded by Robert as responsible for the convul- sant type of ergotism, prevalent in most of the epidemics of ergot-poisoning in northern and eastern Europe. The nature of the substance producing this con- vulsant action, in Robert’s experiments, is one of the points in the pharmacology of ergot which still remains obscure. According to the method of preparation, “cornutin” must have contained the alkaloid now known as “ergotoxinebut this latter does not possess the peculiar action in question. Subsequent observers have failed to obtain from ergot an alkaloid possessing this action, and it is ad¬ mitted by Robert and his pupils that their own recent attempts to obtain it have not succeeded. The preparations commercially obtainable under the name “cor¬ nutin” consist of more or less impure and resinfied mixtures of the known ergot alkaloids, and have not the marked convulsant action. Whether Robert was dealing with a peculiar decomposition product or with an alkaloid occurring ex¬ ceptionally in the batch of ergot with which he worked will probably never be settled; in any case “cornutin” cannot be regarded as a chemical entity or a nor¬ mal ergot constituent. Robert’s third active principle was an acidic resin, named “sphacelinic acid.” This was found to produce the gangrene which formed the predominant feature in the epidemics of ergotism in France, as well as a well- marked gastro-intestinal inflammation. Experimentally the symptoms were seen most typically in fowls. Jacobj’s experiments were directed to a closer chemical characterization of the active principle of Robert’s sphacelinic acid. By ethereal extraction he obtained from ergot a yellow substance, producing gangrene in fowls, to which he gave the name “chrysotoxin.” By extraction with organic acids he separated from this an alkaloidal fraction consisting of a crystalline inert alkaloid, undoubtedly identical with Tanret’s “ergotinine,” but called “sec- alin” by Jacobj, and an amorphous substance, of high physiological activity,