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.
The direct and indirect, the local and remote action of drugs upon the complicated mechanism of a mammalian body is so perplexing that the attempt to ascertain the precise mode of action of a drug by its mere administration, either to a healthy man or to healthy animals, and observation of its effect upon them, is hopeless.
Moreover, the object that we really wish to attain is the power to relieve human suffering, and to avert the premature death due to disease. But in disease we have new factors; changes are produced by it in the functions of the body, and the reaction of the diseased organism to the drugs which we administer is oftentimes different from that of a healthy one. To a man suffering from cholera, for example, enormous doses of drugs have been given without the least effect; and, in the wakefulness of fever, the opium which ought to produce sleep may simply cause excitement and delirium.
As we have seen, the problems put before us are too complicated to be solved directly, and we must therefore simplify them.
This is done in four ways :1st, by observation of the effects of drugs on animals with a simpler organism than our own, such as amoebae or frogs; 2ndly, by applying the drug to some part of an animal body more or less completely separated from the rest, such as, for example, the muscle and nerve, or the heart of a frog separated from the body; and 3rdly, by preventing the drug from reaching one part of the body while it acts on the others, as by ligaturing an artery, as in Bernard's or Kolliker's experiments on curare. 4thly, by producing artificial changes in the relations of the various parts of the body of higher animals, either before or after administration of a drug, as, for example, by dividing the vagi, in order to ascertain how far the change produced in the beats of the heart by a drug is due to its action upon it through these nerves.