Fortschritte der Arzneimittelforschung / Progress in Drug by Dr. D. R. H. Gourley, Dr. K. E. Schulte, Dr. Ingeborg
By Dr. D. R. H. Gourley, Dr. K. E. Schulte, Dr. Ingeborg Mleinek, Dr. H. Jackson, Dr. F. Trendelenburg, Dr. H. R. Ing, Dr. U. C. Dubach (auth.), Dr. Ernst Jucker (eds.)
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Extra resources for Fortschritte der Arzneimittelforschung / Progress in Drug Research / Progrès des recherches pharmaceutiques
The original observations were made with the light microscope and it has been only relatively recently that electron microscope studies, such as those discussed above, have revealed that the same process occurs in other cells on a very minute scale. In spite of the apparent generality of this phenomenon, HOLTER and HOLTZER [151, 152J, who have made many contributions in this area, believe there is not yet enough evidence to conclude that pinocytosis is an important physiological mechanism for the movement of materials across all plasma membranes.
It is not unlikely that when techniques for this kind of study are developed it will be found that inclusion structures account for much of the structural specificity of drugs. 5. Action of Drugs at the Cell Surface Since the plasma membrane of cells is capable of discriminating between even relatively small molecules occurring naturally in the body, it is obvious that the cell surface is a major factor to be considered in a discussion of the action of drug molecules foreign to the body. As a first approximation, it is probable that the only drugs that enter cells are those whose size is small enough to permit passage through aqueous pores in the plasma membrane, or Basic Mechanisms of Drug Action 45 whose chemical structure is sufficiently similar to a normal cell substrate that it may be transported through the plasma membrane via an existing carrier mechanism, or whose lipid solubility is such that they may dissolve in the lipid components of the plasma membrane.
The introduction of bulky substituents on the basic nitrogen atom, such as in isopropylnorepinephrine, produces steric hindrance to the ion-pair formation just mentioned and inhibitory activity begins to appear. This suggests that inhibitory activity is a property inherent in the catechol hydroxyl groups rather than in the cationic head. Consideration of the relative stability of ,8-aminoesters towards hydrolysis led BELLEAU [105, 106J to propose that a phosphate group is the most likely chemical species at the anionic binding site.