Chemical structure and sympathomimetic action of amines / by G. Barger and H.H. Dale.

  • Barger, George, 1878-1939.
Date:
1910
Catalogue details

Licence: Attribution 4.0 International (CC BY 4.0)

Credit: Chemical structure and sympathomimetic action of amines / by G. Barger and H.H. Dale. Source: Wellcome Collection.

Provider: This material has been provided by The Royal College of Surgeons of England. The original may be consulted at The Royal College of Surgeons of England.

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    bility. If the propylamino-bases be left out of consideration the same order holds for the inhibitor activity of the bases, as long as comparison is confined within the limits of an homologous series. But the neces- sity for the omission of the propylamino-bases weakens the significance of the comparison, which further breaks down completely when com- parison is made between members of different series. Thus the comparatively stable methylamino-aceto-catechol has a more powerful inhibitor actiou than the much more easily oxidised methylamino- ethyl-catechol: on the other hand the amino-bases of the pyrogallol series, which are very readily oxidised, have no more inhibitor activity than the comparatively stable amino-bases of the catechol series. It must be concluded, therefore, that instability to oxidising agents is at most a subsidiary factor in determining sympathomimetic activity. The generalisations which can be made from our results are, indeed, but few. All the substances in which we have traced the sympatho- mimetic action are bases. All those which show it characteristically and certainly are, moreover, primary and secondary amines. The quarternary ammonium bases, corresponding to the sympathomimetic amines of the phenolic and catechol series, have a marked activity of a quite different type, closely resembling that of nicotine. In a general way it can be stated, that approximation to adrenine in structure is attended by increase of sympathomimetic activity. The optimum carbon-skeleton, of a primary or secondary amine, for the production of this type of activity, appears to consist of a benzene ring with a side-chain of two carbon atoms, the amino-group and the benzene nucleus being attached each to a different carbon atom of this side- chain. The activity is increased by phenolic hydroxyls in the 3 :4 position relative to the side-chain. When these are both present, but only then, the introduction of an alcoholic hydroxyl, attached to that carbon atom which is linked to the ring, further increases the activity. Inhibitor and motor activity vary to some extent independently when a hydrogen atom of the amino-group is replaced by various alkyl radicles. taking the last point first, it is clear that our results are com- patible with such a proximate conception as that of Elliott1, which, without involving any theory of the intimate nature of the action, postulates the existence of a myoneural junction, the function of which is to receive the nerve-stimulus or chemical stimulant substance, and to which must be ascribed the determination of the response in the 1 loc. cit. and This Journal, xxxv. p. 367. 1907. 4—3