Drug action theory

It is amazing to note that complex processes such as drug binding to protein, activation of cells, and observation of syncytial cellular response should apparently so closely follow a model based on these simple concepts. This was not lost on A. J. Clark in his treatise on drug receptor theory The Mode of Action of Drugs on Cells [4] ... 

MacKay, D. (1977). A critical survey of receptor theories of drag action. In Kinetics of drug action, edited by J. M. Van Rossum, pp. 255—322. Springer-Verlag, Berlin. 

Limbird, L. E., Cell Surface Receptors A Short Course on Theory and Methods, 2nd ed., Nijhoff, Boston, 1996. Pratt, W. B. and Taylor, P., Principles of Drug Action, Churchill Livingstone, New York, 1990 (see, in particular, Chapters 1 and 2). 

Biological response to drug binding, OCCUPANCY THEORY OF DRUG ACTION... 

OCCUPANCY THEORY OF DRUG ACTION OCTAHEDRAL COORDINATION OCTANOL DEHYDROGENASE trans-OCTAPRENYLTRANSTRANSFERASE OCTOPINE DEHYDROGENASE D-Octopine synthase,... 

The mode of action of sulfanilamides became known around 1947, when the structure and biosynthesis of folic acid were elucidated. This compound is built by bacteria from the heterocyclic pteroyl moiety, p-aminobenzoate, and glutamate. p-Aminobenzene-sulfonamide (9.89, sulfanilamide) is a competitive inhibitor of the synthase enzyme, acting as an antimetabolite of p-aminobenzoate. Occasionally, the sulfanilamide can even be incorporated into the modified folate, resulting in an inactive compound and thus an inactive enzyme. This theory, proposed by Woods and Fildes in 1940, became the first molecular explanation of drug action. 

Paton, W. D. M. A Theory of Drug Action Based on the Rate of Drug-Receptor Combination. Proc. R. Soc. London, Ser. B. 1961,154, 21-69. 

In his interesting Edelstein award lecture, presented at the 224th American Chemical Society Meeting in Boston, MA, in August 2002 and entitled To Bond or Not to Bond Chemical Versus Physical Theories of Drug Action , John Parascandola [8] relates the early history of structure-activity relationships. 

Harmer, C.J., Hill, S.A., Taylor, M.J., Cowen, P.J., and Goodwin, G.M. (2003). Toward a neuropsychological theory of antidepressant drug action increase in positive emotional bias after potentiation of norepinephrine activity. American Journal of Psychiatry, 160, 990-992. 

J. Parascandola, To bond or not to bond chemical versus physical theories of drug action , Bull. Hist. Client., 2003, 28, 1-8. 

It was at the turn of the twentieth century that the importance of lipid solubility in drug action was also independently described by Meyer and Overton (the significance of the oil/water partition coefficient was discussed in Chapter 2). The importance of lipid solubility in drug action subsequently became manifested in the lipoid theory of cellular depression. In essence, this theory correlated a pharmacological effect (e.g., CNS depression) with a physical property (i.e., lipid solubility) rather than a structure-activity relationship. In the process, the theory was attempting to explain the diverse chemical structures that exist within the hypnotic and general anesthetic classes of drugs (see Chapter 11). Today, we realize the limitations of the lipoid theory and appreciate that the distinction between physical and chemical factors is illusory, since chemical structure is a determinant of physical properties. 

In this chapter I will look at the main body of research on which current beliefs about the nature and efficacy of the so-called antipsychotic or neuroleptic drugs are based. I will attempt to evaluate whether the data from this and other research supports a disease-based theory of neuroleptic drug action in disorders diagnosed as psychosis or schizophrenia. 

The receptor occupation theory of drug action equates drug effect to receptor occupancy. The intensity of drug effect is proportional to the number of receptors that are occupied by drug and the maximum effect occurs when all receptors are occupied by drug. 

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