The Selectivity of Drugs

1 Introduction.- 1.1 What is Selectivity?.- 1.2 The aims and accomplishments of Selectivity.- References.- 2 Three principles that control selectivity.- 3 Steps in the correlation of structure with biological activity.- 3.1 Introduction.- 3.2 The first correlations.- 3.3 The concept of ‘receptors’.- 3.4 The receptor as an enzyme or permease.- 3.5 The receptor as a nucleic acid.- 3.6 The receptor as a coenzyme, or other small molecule.- 3.7 Other aspects of receptors.- 3.8 Targets that are not necessarily receptors.- 3.9 Regression analysis.- 3.10 Conclusion.- References.- 4 Favourable differences in distribution: the first principle of selectivity.- 4.1 Some examples.- 4.2 Qualitative aspects of distribution.- 4.3 Quantitative aspects of distribution.- 4.4 The permeability of natural membranes.- 4.5 Metabolic change leading to activation.- 4.6 Metabolic change leading to inactivation.- 4.7 Synergism and antagonism.- 4.8 Conclusion.- References.- 5 Favourable differences in biochemistry: the second principle of selectivity.- 5.1 Introduction.- 5.2 Analogous enzymes.- 5.3 More analogous enzymes: the dihydrofolate reductases.- 5.4 Absence of enzymes from one of the species I. The sulphonamides and organophosphates.- 5.5 Absence of enzymes. II Further examples.- 5.6 Metabolite analogues (mostly antagonists).- 5.7 Other utilizable biochemical differences.- 5.8 Conclusion.- References.- 6 Favourable differences in cell structure: the third principle of selectivity.- References.- 7 Acquired resistance to drugs: the loss of selectivity.