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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    injection of various tissue extracts and form the main feature in the clinical picture of the “anaphylactic shock.” At the same time it has been demonstrated that the base can be given hypodermically in small doses without producing bad symptoms, but with marked effect on the uterus. Engeland and Kutscher subsequently isolated from ergot agmatine, the an¬ alogous amine from arginine, and attributed to it a similar action. According to Dale and Laidlaw the effect of agmatine is very weak, and it cannot contribute in any significant degree to the action of ergot. It is not suggested, of course, that all the constituents possessing a physiological action of any kind, which occur in any sample of ergot or its extracts, have been isolated and identified. On the contrary, it has been obvious, from the latter por¬ tion especially of Barger and Dale’s work on this subject, that the casual oc¬ currence of unusual bases is only to be expected in extracts of a fungus which shows many similarities in its action to certain putrefactive bacteria. It is even uncertain, in any particular case, how much of the active amine constituent must be attributed to the metabolism of the ergot itself, how much to superadded pu¬ trefactive changes occurring either before or during extraction. What is quite certain is that good, dry ergot contains not merely ergotoxine, but also the bases in question, though the proportion of these latter may well be increased in the preparation of such a product as the Liquid Extract of the B. P., and still more so in the dialysed preparations. It may further be claimed that the substance re¬ sponsible for each of the various physiological actions, hitherto suggested as a basis of standardization, has been isolated and identified. The effect on the cock’s- comb was given practical application for standardization by Houghton, who gave details by observance of which a quantitative indication was obtainable. This has been recently verified by Edmunds and Hale. This action, like the “vaso- metor reversal” described by Dale, is due to ergotoxine, and while the practice of different observers may lead them to prefer one or another of these methods, they are testing, in either case, for ergotoxine only. When the measurement of pressor effect, in dog or cat, as recommended by Wood and by Cronyn and Henderson in America, and by Dixon, Goodall and others in England, is adopted as an index of activity, the measurement appears to be one of ergotoxine -j-“tyr- amine” in the case of the Liquid Extract of the British Pharmacopoeia, Kehrer’s method, again, if a cat’s uterus be used, is apparently a measurement of “ergam- ine” content only; on the other hand, the isolated guinea-pig’s uterus is exquis¬ itely sensitive to ergotoxine as well as to ergamine.” It will doubtless be possible by a combination of methods to work out a rational system of ergot standardiza¬ tion when it is once decided which of the principles are therapeutically desirable and in what relative proportions they should occur. What is needed above all for the settlement of this aspect of the ergot-problem is an accumulation of ac¬ curate clinical observation with the pure active principles. Meanwhile it may be said that results hitherto available appear to point to the superiority of a prepar¬ ation containing the three chief active principles in appropriate proportions, as compared with any one of them separately. It should be further remembered that ergotoxine is the only one of them for which ergot is needed. The others are much more easily obtained by synthesis in the laboratory, and it may be as-