The action of certain esters and ethers of choline and their relation to muscarine / by H.H. Dale.

  • Dale, Henry H. (Henry Hallett), 1875-1968.
Date:
[1914?]
Catalogue details

Licence: In copyright

Credit: The action of certain esters and ethers of choline and their relation to muscarine / by H.H. Dale. Source: Wellcome Collection.

    4/48 (page 148)
    ester of nitrous acid, HO • N(CH3)3 ■ CH2CH2 ■ O - NO and not, as supposed by Schmiedeberg and Harnack, an aldehyde. This observation led us to consider the possibility that the true, natural muscarine, from Amanita Muscaria, might be also a choline-ester, although the supposition would involve a revision of the formula, based by Schmiedeberg and Harnack on their analyses. To test this idea we examined several choline-esters, and one of these, the nitric acid ester, HON(CH3)3CH2CH2 0-N02, was found to resemble true muscarine in action more closely than does the nitrous acid ester—the so-called “pseudo¬ muscarine.” The difference was still clearly marked, however, in that nitric, like the nitrous acid ester, has an action of the nicotine-curare type on the atropinised frog, which is not shown by natural muscarine. Meanwhile experiments on the stability to hydrolysing agents of the activity of an Amanita extract had considerably weakened the probability of muscarine being a choline ester. Brief boiling with 1 per cent caustic alkali affected the activity of the extract hardly at all. The more stable ethers of choline were, therefore, investigated, and in the ethyl-ether, H0.N(CH)3CH2.CH2.0. C2H5, we found a substance showing a closer resemblance to mus¬ carine in action than any other of the whole series of derivatives as yet examined from this point of view. The only point of dif¬ ference was, again, the possession by the ethyl-ether of a nicotine- curare action on the atropinised frog; but this was quite sufficient to exclude its identification with muscarine. It seems doubtful at present whether we shall succeed in get¬ ting further light on the structure of the true muscarine, unless we can procure a sufficient supply of the substance for a direct investigation. Meanwhile it seems desirable to give a compara¬ tive account of the action of the chlorine-derivatives which our search has led us to examine, many of them being substances of extraordinary potency, related very closely in their physiological properties, and, in al probability, not distantly in their chemical structure to muscarine itself. Of the substances examined, only a few, and those the more active, were made the subject of at all a complete physiological