Responses of isolated bronchial muscle to ganglionically active drugs / by D.F. Hawkins and W.D.M. Paton.

  • Hawkins, D. F. (Denis Frank)
Date:
[1958?]
Catalogue details

Licence: In copyright

Credit: Responses of isolated bronchial muscle to ganglionically active drugs / by D.F. Hawkins and W.D.M. Paton. Source: Wellcome Collection.

    6/28 (page 198)
    Nicotinic alkaloids. We have already mentioned that nicotine tends to block its own action on the tracheal muscle (Fig. 16). It is known that related alkaloids can antagonize other responses to nicotine (Dale & Laidlaw, 1911-12) and the action of a number of these alkaloids was examined. It was found that lobeline 1 pg/ml., coniine 0-5 pg/ml., cytisine 5 fig/ml., sparteine 0-5 /xg/ml. and anagyrine 2 gg/ml. all abolished the nicotine response. These alkaloids did not affect bronchodilator responses to adrenaline or noradrenaline. Sympatholytic drugs. Since the response to nicotine was bronchodilator, the ganglion cells concerned might be supposed to mediate the response by liberat¬ ing sympathin at their post-ganglionic endings. Some difficulty was expected in testing this conclusion with sympatholytic drugs, for two reasons. It is commonly held that such drugs are only effective against the stimulant actions of adrenaline; and the pharmacological effect of many of these drugs is a complex mixture of sympatholytic, sympathomimetic, and potentiating actions. It was therefore judged necessary first to examine a number of sympatholytic drugs in order to select drugs which could be used to antagonize, if possible differentially, the relaxant effects of adrenaline and noradrenaline on the tracheal chain. The results of this survey are shown in Table 1. It was found that ergo- toxine would antagonize the bronchodilator action of adrenaline, but not that of noradrenaline. This drug is unsatisfactory to use because of its low solubility; it tends to be precipitated after addition to the bath. It was therefore added to the bath as a fine aqueous suspension to give a final ‘concentration5 of 100 jag/ml.; under these conditions the drug was precipitated, but presumably gave a saturated solution. Ergotoxine was unsuitable for quantitative work, but ergotamine and dihydroergotamine both antagonized adrenaline over fairly wide ranges of concentration. The results with these alkaloids against noradrenaline were rather irregular. In a single test, ergometrine was inactive against both amines. Prosympal (883 F) and phentolamine were both inactive against the amines in the concentrations tested. Dibenamine and dibenzyline showed mixed potentiating and antagonistic actions, and became precipitated in the bath. Mepyramine was in general inactive against adrenaline but potentiated noradrenaline in two experiments. Tolazoline potentiated adren¬ aline at most of the levels of dose tested. Ergotoxine used as just described, to give a concentration in the bath of something less than 100 fig/ml., abolished the bronchodilator response of the guinea-pig trachea to nicotine, and also the dilator response to adrenaline, leaving the response to noradrenaline unaffected (Fig. 4a). This indicated that the nerve endings mediating the nicotine response were adrenergic, and suggested that the transmitter was adrenaline itself. In a number of experiments the actions of low concentrations of dihydro¬ ergotamine and ergotamine on responses to adrenaline and nicotine were