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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    which he called “sphacelotoxin.” This latter, for reasons which now appear to be inadequate, Jacobj described as a non-nitrogenous resin, in spite of the fact that his analyses of “secalintoxin” (i. e. “secalin”-|-“sphacelotoxin’') and of secalin (=ergotinine) show identical percentages of nitrogen. With regard to the therapeutic bearing of these investigations, Jacobj regarded sphacelotoxin as the bearer of the therapeutic as well as the toxic properties of ergot. Robert, at one stage of his investigation, attributed the therapeutic ef¬ fect on uterine activity to “sphacelinic acid,” at another to “cornutin.” Probably the main effect of these researches on the course of ergot investigations was the establishment of the cock’s-comb test as an empirical measure of the activity of the drug. From the chemical point of view the subject was left, in 1897, in a far worse position than that to which Tanret had brought it in 1875, and the of¬ ficial pharmacological teaching concerning ergot became once more a matter of complicated terminology for ill-defined substances. This was the state of affairs when, in 1904, an investigation wras begun at the Wellcome Physiological Research Laboratories. Those responsible for this soon came to the conclusion that it would be fruitless, in the first instance, to search for a principle endowed with all the physiological actions which, at one time or another, had been attributed to ergot, and associated, on inadequate evidence, with its therapeutic value. The first step, rather, must be to take some charac¬ teristic action, which could be regarded as probably the effect of one active con¬ stituent, and endeavor to ascertain the nature of that constituent. It would then be possible, if a chemically pure principle were obtainable, to investigate its re¬ lation to other types of action, and to search further for other principles, if it became clear that more than one was involved. It seemed natural, at that stage in the history of the drug, to start by examining and further analyzing the action of preparations made according to the methods of Robert and Jacobj. The re¬ sults of this preliminary investigation are embodied in the first paper by H. H. Dale, in which a highly characteristic effect on the function of the true sympa¬ thetic system is described. All the preparations tested had a potent stimulating action on plain muscle, succeeded by a paralysis of motor sympathetic effects, while the inhibitor actions of the same system were left unaffected. The most readily observed instance of this action was the fall of blood-pressure resulting from injection of the suprarenal active principle, in place of its normal, typical, pressor action. It may be noted, in passing, that this so-called ‘Vasomotor re¬ versal” test has been the subject of some criticism by those who have attempted to use it as an indication of ergot-activity in general. It is desirable to make it clear that its originators never claimed for it any value except as a test for a particular active principle, and that it is not surprising that others have failed to find it applicable to extracts owing their activity chiefly to other substances. The search for the substance producing this action was conducted by G. Barger of the Wellcome Physiological Research Laboratories, working in conjunction with F. H. Carr of the Wellcome Chemical Works, Dartford, their results being con¬ stantly controlled by Dale’s physiological experiments. They were soon able to identify the active substance as an alkaloid, closely resembling Tanret’s ergotinine in many of its chemical properties, but differing from it in solubility and in the