This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
In experiments regarding the effect of drugs upon the respiration, the voluntary influence of the brain is excluded by the use of ether, chloroform, opium, or chloral, or by section of the crura cerebri. In the case of such poisons as cause sickness allowance must be made for the effect of gastric irritation. It will usually be found that before vomiting occurs the respiratory movements are very rapid, but they become slower after vomiting has taken place. As the chief afferent fibres from the stomach are contained in the vagus, the effect of irritation of the gastric, as well as of other fibres contained in these nerves, is prevented by their division. Sometimes the action of a drug on the peripheral ends of the vagus and upon its roots in the medulla may produce exactly opposite effects upon the respiration. Thus atropine appears to lessen the excitability of the respiratory fibres of the vagus, while it stimulates the respiratory centre. Such an action may be to a certain extent inferred from the respiration becoming slower almost immediately after the injection of the drug into the jugular vein, and while it is still passing through the lungs, and by this slowing being quickly succeeded by acceleration when the drug begins to circulate through the medulla.
There are two kinds of experiment by which such a conclusion may be tested. The one is to apply the drug first to the medulla by injecting it into the carotid artery, and seeing whether acceleration occurs at once and afterwards becomes less when the drug has had time to pass round again to the lungs. The other way is to divide the vagi before the injection and observe the effect. Any alteration in the respiration in the way of either quickening or slowing which the drug produced in the uninjured animal should remain the same after division of the vagi if its effect were due to its action on the medulla, but will be absent if it were due to an action upon the peripheral ends of the vagi.
1 Brown-Sequard, Archives of Scientific and Practical Medicine, p. 94.
2 Sitzungsber. der Wien. Acad., vol. lxviii. Abt. 3, p. 255.
This method was introduced into pharmacological research by Yon Bezold in his admirable research on atropine, and it is the one usually employed.
There is one fallacy, however, which must not be entirely lost sight of, which is, that after division of the vagi the nerves which remain in connection with the respiratory centre have chiefly a slowing action on the respiration; and thus a drug which really renders the respiratory centre more susceptible to reflex influences might seem to have a depressing action upon it.
While atropine injected into the jugular vein seems to produce first a slowing of the respiration, due to its paralysing action on the vagus ends, and afterwards a progressive quickening as more of it is carried out of the lungs into the medulla, phy-sostigmine, muscarine, and veratrine have an opposite action, quickening the respiration at first by their stimulating action on the vagus ends, and afterwards slowing it by their action on the medulla.
In the action of veratrine upon the pulmonary branches of the vagus we may notice a resemblance to the stimulant action which, as already mentioned, it exerts upon the nerves of ordinary sensation. If the sensory branches of the vagus are affected by drugs in a somewhat similar way to those of ordinary sensation, as the action of veratrine might lead us to imagine, we should expect them to be much stimulated also by aconite, and, indeed, according to Boehm and Ewers, this is the case. The respiratory changes produced by aconite are regarded by them as due, in part, to irritation of the peripheral ends of the vagus, and disappear on section of the vagi or the administration of atropine.