The first recordings of pharmacological effects

Abstract

In mid-nineteenth century Germany, the graphic recording of drug effects began simultaneously with the development of pharmacology as an independent science. With the first recording device, the kymograph, drug effects were recorded and compared. A new method for keeping an isolated organ alive facilitated research into the organ's modes of action. Together, these two physiological methods facilitated study of the effects of drugs on organ function. Drug characteristics were discovered and many crude drugs were standardized. Many physiological processes were discovered using these innovative methods. A good example is provided by digitalis, the potency of which varied widely. Digitalis was of great importance in the discovery and treatment of cardiac arrhythmias. Subsequently, many physiological processes were discovered using these innovative approaches to drug research.Pharmacology is a relatively young science, arising from the great progress in chemistry and physiology of the nineteenth century [1,2]. At the start of the nineteenth century, chemistry made it possible to isolate active substances from medicinal plants, starting with morphine in 1806 [3]. Physiology provided the methodology for pharmacology to become an independent medical discipline. The French physiologist François Magendie performed one the first pharmacological experiments with the strychnos tree, from which he isolated the alkaloid strychnine. His successor, Claude Bernard, used active substances, e.g. the Indian arrow poison, curare, as 'scalpels chimique' for the 'dissection' of physiological processes. In this way he demonstrated that curare acted upon the connection of the nerve with the muscle, the neuromuscular junction [4,5].Knowledge from chemistry and physiology together formed the basis for experimental pharmacology. Rudolf Buchheim, the first professor of pharmacology, turned drug discovery from an empirical search for cures into a science [6]. He claimed that the effects of a drug could best be studied by isolating the substance, investigating its chemical composition and correlating the chemistry of the drug with the changes it caused in the function of organs.He also formulated the two main questions for drug research: 'in which way and to what extent are drugs altered by the body, and in which way and to what extent do they in turn alter the body's function?' [7]. Such examinations were to be carried out with the same methods as were used in physiology [8]. Oswald Schmiedeberg, Buchheim's most prominent disciple, set up a new laboratory for experimental pharmacology in Strasbourg, then a German city. He was recommended for his post by Carl Ludwig, the great physiologist from Leipzig. Preceding his appointment in Strasbourg, Schmiedeberg had been trained in experimental methodology in Ludwig's institute in Leipzig [9,10]. Buchheim, Schmiedeberg and Ludwig adapted the research methods of physiology and brought modern pharmacology into being.The two most important physiological methods introduced in early pharmacology were the...

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