Methods of General Pharmacology

The aim of general pharmacology is to discover the nature of the chemical reactions that occur when drugs act upon cells, and the obvious line of approach is to apply the methods used in physical chemistry, but any such attempt at once reveals the following fundamental difficulties. In the first place the simplest cell is a far more complex structure than any system studied by physical chemists. This complexity greatly reduces the significance of simple quantitative estimations. Even if it is known that the fixation of a certain number of molecules by a cell produces a certain derangement of function, yet we still do not know what proportion of the drug fixed is responsible for the actions observed. In the second place the entrance of a drug into a cell is in most cases a complex process involving adsorption and diffusion and finally resulting in a response which is measured. It is obvious that the time relations between the introduction of the drug and the appearance of the biological response provide extremely uncertain information, because the delay measured may be due to so many different causes. In the third place, investigations are limited by the fact that normal functions of living cells can only be maintained within a narrow range of physico-chemical conditions, hence it is not possible to test the validity of possible physico-chemical explanations over wide ranges of temperature etc. Fourthly, it must be remembered that all living cells show both static and dynamic variation. A uniform population of cells is an unknown phenomenon, and living cells are usually changing in some manner, a fact which makes it difficult to obtain accurate controls.